Wednesday, October 19, 2016

CellCept Suspension



Pronunciation: MYE-koe-FEN-oh-late MOE-fe-til
Generic Name: Mycophenolate Mofetil
Brand Name: CellCept

CellCept Suspension weakens your immune system, which may decrease your ability to fight illness or infection. It may also increase the risk of certain types of cancer (eg, lymphoma). Use CellCept Suspension only under close medical supervision.


CellCept Suspension may cause birth defects or fetal death if taken during pregnancy. Women who may become pregnant must use an effective form of birth control while they are taking CellCept Suspension.





CellCept Suspension is used for:

Preventing organ rejection following kidney, liver, or heart transplants. CellCept Suspension is used in combination with other medicines. It may also be used for other conditions as determined by your doctor.


CellCept Suspension is an immunosuppressant. It works by decreasing the activity of certain cells that make up part of the immune system to help reduce the risk of organ transplant rejection.


Do NOT use CellCept Suspension if:


  • you are allergic to any ingredient in CellCept Suspension or to mycophenolic acid

  • you are taking azathioprine, cholestyramine, colestipol, or another medicine that contains mycophenolate or mycophenolic acid

  • you are taking norfloxacin and metronidazole together

  • you have a rare hereditary deficiency of hypoxanthine guanine phosphoribosyl-transferase (HGPRT), such as Lesch-Nyhan syndrome or Kelley-Seegmiller syndrome

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



Before using CellCept Suspension:


Some medical conditions may interact with CellCept Suspension. 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 immune system problems or have been taking another medicine that may suppress your immune system

  • if you have stomach or intestinal problems (eg, ulcers), kidney problems, or phenylketonuria (PKU)

  • if you have a personal or family history of skin cancer, blood cancer (eg, lymphoma), or other blood problems

  • if you are scheduled for a vaccination

  • if you will be in close contact with a person who has shingles, another type of herpes infection, or cytomegalovirus (CMV) infection

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


  • Acyclovir, azathioprine, ganciclovir, mycophenolic acid, or probenecid because they may increase the risk of CellCept Suspension's side effects

  • Cholestyramine, colestipol, cyclosporine, norfloxacin along with metronidazole, or rifampin because they may decrease CellCept Suspension's effectiveness

  • Live vaccines or oral contraceptives because their effectiveness may be decreased by CellCept Suspension

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


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


  • CellCept Suspension comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get CellCept Suspension refilled.

  • Take CellCept Suspension by mouth on an empty stomach at least 1 hour before or 2 hours after eating unless your doctor tells you otherwise.

  • Shake well before each use.

  • Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.

  • Do not take an antacid that has aluminum or magnesium in it within 3 hours of taking CellCept Suspension.

  • If you take a calcium-free phosphate binder (eg, sevelamer), take it 2 hours after taking CellCept Suspension.

  • If you miss a dose of CellCept Suspension, 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 CellCept Suspension.



Important safety information:


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

  • Women who may become pregnant must have a negative pregnancy test within 1 week before starting CellCept Suspension.

  • Women who may become pregnant must use 2 effective forms of birth control for 4 weeks before they start CellCept Suspension, during treatment, and for 6 weeks after they stop CellCept Suspension. Check with your doctor if you have any questions about effective birth control.

  • Hormonal birth control (eg, birth control pills) may not work as well while you are taking CellCept Suspension. Discuss any questions or concerns with your doctor.

  • CellCept Suspension may increase your risk of developing certain types of cancer (eg, lymphoma, skin cancer). Avoid the sun, sunlamps, or tanning booths while you take CellCept Suspension. Use a sunscreen or wear protective clothing if you must be outside for more than a short time. Tell your doctor right away if you notice a change in the size or color of a mole or if you develop any new or unusual skin growths.

  • CellCept Suspension may lower the ability of your body to fight infection and may increase the risk of severe or fatal infections. Avoid contact with people who have colds, shingles, other herpes infections, cytomegalovirus (CMV), or other infections. Tell your doctor right away if you notice signs of infection like fever, sore throat, rash, or chills.

  • Some patients treated with CellCept Suspension have developed severe and sometimes fatal infections, such as progressive multifocal leukoencephalopathy (PML) or severe kidney problems associated with BK virus infection. Discuss any questions or concerns with your doctor.

  • Tell your doctor right away if you notice symptoms of PML (eg, confusion or disorientation; depression; changes in thinking, strength, or vision; one-sided weakness; trouble walking or talking; loss of balance or coordination).

  • Tell your doctor right away if you notice symptoms of kidney problems (eg, change in the amount of urine produced, difficult or painful urination, blood in the urine). In kidney transplant patients, BK virus infection may cause loss of the transplanted kidney. Discuss any questions or concerns with your doctor.

  • Some patients treated with CellCept Suspension have developed a type of anemia called pure red cell aplasia (PRCA). Contact your doctor right away if you experience severe or persistent tiredness or weakness, sluggishness, or unusually pale skin.

  • CellCept Suspension may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.

  • Diarrhea may occur with CellCept Suspension. If you develop diarrhea, check with your doctor or pharmacist about ways to lessen this effect. Do not stop CellCept Suspension without talking with your doctor.

  • Do not change brands or doseforms (eg, tablets, suspension, injection) of CellCept Suspension without talking with your doctor.

  • Do not receive a live vaccine (eg, measles, mumps) while you are using CellCept Suspension. Talk with your doctor before you receive any vaccine.

  • Phenylketonuria patients - CellCept Suspension has phenylalanine in it.

  • Lab tests, including complete blood cell counts and kidney function, may be performed while you use CellCept Suspension. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

  • Use CellCept Suspension with caution in the ELDERLY; they may be more sensitive to its effects, especially infection, stomach or intestinal bleeding, and trouble breathing.

  • Caution is advised when using CellCept Suspension in CHILDREN; they may be more sensitive to its effects.

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


Possible side effects of CellCept Suspension:


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:



Anxiety; back pain; constipation; cough; diarrhea; dizziness; headache; loss of appetite; mild stomach pain; mild tiredness or weakness; nausea; tremor; trouble sleeping; upset stomach; 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); blood in the urine; bloody or black stools; change in the amount of urine produced; chest pain or pounding in the chest; fainting; irregular heartbeat; mental or mood changes (eg, abnormal thinking); night sweats; numbness, tingling, or swelling of the arms, legs, hands, ankles, or feet; severe headache, dizziness, or blurred vision; severe vomiting or stomach pain; shortness of breath; sluggishness; swollen glands; symptoms of infection (eg, fever, chills, cough, sore throat); symptoms of urinary tract infection (eg, difficult, frequent, or painful urination; lower stomach or back pain); unusual bruising or bleeding; unusual skin lumps or growths; unusual tiredness or weakness; unusual weight loss; unusually pale skin; vomiting blood that looks like coffee grounds; white patches in the mouth or throat; yellowing of the skin or eyes.



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: CellCept 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 (http://www.aapcc.org ), or emergency room immediately. Symptoms may include diarrhea; nausea; vomiting.


Proper storage of CellCept Suspension:

Store CellCept Suspension at 77 degrees F (25 degrees C) in a tightly closed container. Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Storage in a refrigerator, between 36 and 46 degrees F (2 and 8 degrees C), is acceptable. Do not freeze. Discard any unused portion after 60 days. Store away from heat, moisture, and light. Do not store in the bathroom. Keep CellCept Suspension out of the reach of children and away from pets.


General information:


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

  • CellCept Suspension 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 CellCept Suspension. 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 CellCept resources


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


Compare CellCept with other medications


  • Inflammatory Bowel Disease
  • Nephrotic Syndrome
  • Organ Transplant, Rejection Prophylaxis

Cepacol Viractin


Generic Name: tetracaine (Topical application route)

TE-tra-kane

Commonly used brand name(s)

In the U.S.


  • Cepacol Viractin

  • Pontocaine

In Canada


  • Supracaine

Available Dosage Forms:


  • Cream

  • Ointment

  • Gel/Jelly

  • Solution

Therapeutic Class: Anesthetic, Local


Chemical Class: Amino Ester


Uses For Cepacol Viractin


Tetracaine is used in different parts of the body to cause numbness or loss of feeling in some patients before having a medical test or procedure.


Tetracaine belongs to a group of medicines known as topical local anesthetics. It deadens the nerve endings in the skin. This medicine does not cause unconsciousness as general anesthetics do when used for surgery.


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


Before Using Cepacol Viractin


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


No information is available on the relationship of age to the effects of tetracaine in the pediatric population. Safety and efficacy have not been established.


Geriatric


No information is available on the relationship of age to the effects of tetracaine in geriatric patients.


Interactions with Medicines


Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.


Interactions with Food/Tobacco/Alcohol


Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.


Other Medical Problems


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


  • Brain or spinal problems or

  • Eye problems or

  • Heart and blood vessel problems—Use with caution. May make these conditions worse.

  • Infection at or near the place of application or

  • Large sores, broken skin, or severe injury at the area of application—The chance of side effects may be increased.

Proper Use of tetracaine

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


A nurse or other trained health professional will give you this medicine. This medicine is for use on the skin only.


Be careful not to get any of this medicine in your nose, mouth, and especially in your eyes, because it can cause severe eye irritation. If any of the medicine does get into these areas especially the eyes, wash it with water and check with your doctor right away.


Precautions While Using Cepacol Viractin


It is very important that your doctor check you closely for any problems or unwanted effects that may be caused by this medicine.


Stop using this medicine and check with your doctor right away if you have a skin rash, burning, stinging, swelling, or irritation of your skin.


Do not use cosmetics or other skin care products on the treated skin areas.


Cepacol Viractin 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 or nurse immediately if any of the following side effects occur:


Incidence not known
  • Blurred vision

  • chest pain or discomfort

  • confusion

  • dizziness

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

  • fainting

  • fast or irregular heartbeat

  • lightheadedness or fainting

  • no blood pressure or pulse

  • no breathing

  • numbness

  • seizures

  • shakiness in the legs, arms, hands, or feet

  • shortness of breath

  • slow or irregular heartbeat

  • stopping of heart

  • sweating

  • trembling or shaking of the hands or feet

  • 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
  • Continuing ringing or buzzing or other unexplained noise in the ears

  • fear or nervousness

  • hearing loss

  • restlessness

  • sleepiness

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.


More Cepacol Viractin resources


  • Cepacol Viractin Support Group
  • 1 Review for Cepacol Viractin - Add your own review/rating


Compare Cepacol Viractin with other medications


  • Allergic Urticaria
  • Cold Sores
  • Local Anesthesia
  • Skin Rash
  • Urticaria

clorazepate


klor-AZ-e-pate


Commonly used brand name(s)

In the U.S.


  • Gen-Xene

  • Tranxene

  • Tranxene-SD

  • Tranxene T-Tab

Available Dosage Forms:


  • Tablet

  • Tablet, Extended Release

  • Capsule

Therapeutic Class: Antianxiety


Pharmacologic Class: Benzodiazepine, Long Acting


Uses For clorazepate


Clorazepate is used to relieve symptoms of anxiety and alcohol withdrawal. clorazepate may also be used to treat partial seizures.


Clorazepate is a benzodiazepine. Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants, which are medicines that slow down the nervous system.


clorazepate is available only with your doctor's prescription.


Before Using clorazepate


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 clorazepate, the following should be considered:


Allergies


Tell your doctor if you have ever had any unusual or allergic reaction to clorazepate 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 clorazepate in children younger than 9 years of age. Safety and efficacy have not been established.


Geriatric


Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of clorazepate in the elderly. However, severe drowsiness, dizziness, confusion, clumsiness, or unsteadiness are more likely to occur in the elderly, who are usually more sensitive than younger adults to the effects of clorazepate. Elderly patients may require a lower dose to help reduce unwanted effects.


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 clorazepate, 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 clorazepate 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

  • Amobarbital

  • Anileridine

  • Aprobarbital

  • Butabarbital

  • Butalbital

  • Carisoprodol

  • Chloral Hydrate

  • Chlorzoxazone

  • Codeine

  • Dantrolene

  • Ethchlorvynol

  • Fentanyl

  • Fospropofol

  • Hydrocodone

  • Hydromorphone

  • Levorphanol

  • Meperidine

  • Mephenesin

  • Mephobarbital

  • Meprobamate

  • Metaxalone

  • Methocarbamol

  • Methohexital

  • Morphine

  • Morphine Sulfate Liposome

  • Omeprazole

  • Oxycodone

  • Oxymorphone

  • Pentobarbital

  • Phenobarbital

  • Primidone

  • Propoxyphene

  • Remifentanil

  • Secobarbital

  • Sodium Oxybate

  • Sufentanil

  • Tapentadol

  • Thiopental

  • Zolpidem

Using clorazepate 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.


  • Amprenavir

  • Ginkgo

  • St John's Wort

  • Theophylline

Interactions with Food/Tobacco/Alcohol


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


Other Medical Problems


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


  • Drug abuse or dependence, or history of—Dependence on clorazepate may develop.

  • Glaucoma, narrow angle or

  • Mental illness or depression—Should not be used in patients with these conditions.

  • Kidney disease or

  • Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of clorazepate


Take clorazepate 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.


clorazepate should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.


clorazepate may be used with other seizure medicines. Keep using all of your seizure medicines unless your doctor tells you to stop.


Dosing


The dose of clorazepate 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 clorazepate. 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 (tablets):
    • For anxiety:
      • Adults—30 milligrams (mg) per day, taken in divided doses. Your doctor may adjust your dose if needed.

      • Older adults—At first, 7.5 to 15 mg per day, taken at bedtime or in divided doses. Your doctor may increase your dose if needed.

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


    • For symptoms of alcohol withdrawal:
      • Adults—At first, 30 milligrams (mg), followed by 30 to 60 mg in divided doses. Your doctor will set up a schedule that will gradually reduce your dose until your symptoms improve. The dose is usually not more than 90 mg per day.

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


    • For control of seizures:
      • Adults and teenagers—At first, 7.5 milligrams (mg) three times a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 90 mg per day.

      • Children 9 to 12 years of age—At first, up to 7.5 mg two times a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 60 mg per day.

      • Children younger than 9 years of age—Use and dose must be determined by your doctor.



Missed Dose


If you miss a dose of clorazepate, 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 clorazepate


It is very important that your doctor check the progress of you or your child at regular visits to see if the medicine is working properly. Blood tests may be needed to check for any unwanted effects.


Using clorazepate while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away. Your doctor may want you to join a pregnancy registry for patients taking a seizure medicine.


clorazepate may cause some people, especially older persons, to become drowsy, dizzy, lightheaded, clumsy or unsteady, or less alert than they are normally. Also, clorazepate may cause double vision or other vision problems. Make sure you know how you react to clorazepate before you drive, use machines, or do anything else that could be dangerous if you are not alert or able to think or see well.


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


Do not stop taking clorazepate without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent a worsening of your condition and reduce the possibility of withdrawal symptoms, such as convulsions (seizures), hallucinations, nausea or vomiting, stomach or muscle cramps, tremors, or unusual behavior.


clorazepate may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you, your child, or your caregiver notice any of these side effects, tell your doctor or your child's doctor right away.


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


clorazepate 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:


Less common
  • Bladder pain

  • bloody or cloudy urine

  • difficult, burning, or painful urination

  • frequent urge to urinate

  • lower back or side pain

  • shakiness and unsteady walk

  • slurred speech

  • trembling or shaking of the hands or feet

  • unsteadiness, trembling, or other problems with muscle control or coordination

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


Symptoms of overdose
  • Change in consciousness

  • drowsiness

  • loss of consciousness

  • relaxed and calm

  • sleepiness

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:


Less common
  • Blurred vision

  • diarrhea

  • discouragement

  • dizziness

  • double vision

  • dry mouth

  • feeling sad or empty

  • headache

  • indigestion

  • irritability

  • loss of appetite

  • loss of interest or pleasure

  • mental confusion

  • nausea or vomiting

  • nervousness

  • passing of gas

  • seeing double

  • skin rash

  • sleeplessness

  • stomach pain, fullness, or discomfort

  • trouble with concentrating

  • trouble with sleeping

  • unable to sleep

  • unusual tiredness or weakness

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: clorazepate 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.


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More clorazepate resources


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


  • clorazepate Concise Consumer Information (Cerner Multum)

  • Clorazepate Prescribing Information (FDA)

  • Clorazepate MedFacts Consumer Leaflet (Wolters Kluwer)

  • Clorazepate Dipotassium Monograph (AHFS DI)

  • Tranxene T-Tab Prescribing Information (FDA)



Compare clorazepate with other medications


  • Alcohol Withdrawal
  • Anxiety
  • Seizure Prevention

Condasin


Generic Name: guaifenesin and hydrocodone (gwye FEN e sin and HYE droe KOE done)

Brand Names: A-Cof DH, Canges-XP, Codiclear DH, Condasin, Cotuss V, Execlear, Extendryl HC, Hycotuss Expectorant, Hydrocod-GF, Kwelcof, Monte-G HC, Narcof, Pancof XP, Pneumotussin 2.5, Relasin-HCX, Touro HC, Tussicle, Tusso-DF, Vi-Q-Tuss, Vitussin Expectorant, Xpect-HC, Z-Cof HCX


What is Condasin (guaifenesin and hydrocodone)?

Guaifenesin is an expectorant. It helps loosen congestion in your chest and throat, making it easier to cough out through your mouth.


Hydrocodone is a narcotic cough suppressant.


Guaifenesin and hydrocodone is used to treat cough and reduce chest congestion caused by the common cold, flu, or allergies.


Guaifenesin and hydrocodone may also be used for purposes not listed in this medication guide.


What is the most important information I should know about Condasin (guaifenesin and hydrocodone)?


This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of guaifenesin and hydrocodone. Tell your doctor if you regularly use other medicines that make you sleepy (such as other cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by guaifenesin and hydrocodone. Hydrocodone may be habit-forming and should be used only by the person it was prescribed for. Keep the medication in a secure place where others cannot get to it.

What should I discuss with my healthcare provider before taking Condasin (guaifenesin and hydrocodone)?


Hydrocodone may be habit forming and should be used only by the person it was prescribed for. Never share this medication with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Do not use this medicine if you are allergic to hydrocodone or guaifenesin.

To make sure you can safely take guaifenesin and hydrocodone, tell your doctor if you have any of these other conditions:



  • liver or kidney disease;




  • asthma;




  • urination problems;




  • an enlarged prostate;




  • a thyroid disorder;




  • seizures or epilepsy;




  • gallbladder disease;




  • a head injury; or




  • Addison's disease.




FDA pregnancy category C. It is not known whether this medication will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. Guaifenesin and hydrocodone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Condasin (guaifenesin and hydrocodone)?


Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.


Guaifenesin and hydrocodone can be taken with or without food.


Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.


Call your doctor if your symptoms do not improve, or if they get worse. Store at room temperature away from moisture and heat.

Keep track of the amount of medicine used from each new bottle. Guaifenesin and hydrocodone is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.


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 extreme drowsiness, sweating, pinpoint pupils, nausea, vomiting, dry mouth, confusion, cold and clammy skin, muscle weakness, fainting, weak pulse, slow heart rate, seizure (convulsions), weak or shallow breathing, or breathing that stops.


What should I avoid while taking Condasin (guaifenesin and hydrocodone)?


This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of guaifenesin and hydrocodone.

Ask a doctor or pharmacist before using any other cough, cold, allergy, pain, or sleep medicine. Guaifenesin is contained in many combination medicines. Taking certain products together can cause you to get too much guaifenesin. Check the label to see if a medicine contains guaifenesin.


Condasin (guaifenesin and hydrocodone) 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. Stop using this medication and call your doctor at once if you have a serious side effect such as:

  • slow heart rate, weak or shallow breathing;




  • feeling like you might pass out;




  • confusion, fear, unusual thoughts or behavior;




  • seizure (convulsions); or




  • urinating less than usual or not at all.



Less serious side effects may include:



  • dizziness, drowsiness;




  • nausea, vomiting, upset stomach;




  • blurred vision;




  • constipation;




  • dry mouth; or




  • sweating.



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 will affect Condasin (guaifenesin and hydrocodone)?


Tell your doctor if you regularly use other medicines that make you sleepy (such as other cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by guaifenesin and hydrocodone.

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



  • antidepressants such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan), nortriptyline (Pamelor), and others;




  • atropine (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), glycopyrrolate (Robinul), mepenzolate (Cantil), methscopolamine (Pamine), or scopolamine (Transderm-Scop);




  • bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare);




  • a bronchodilator such as ipratropium (Atrovent) or tiotropium (Spiriva); or




  • irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Anaspaz, Cystospaz, Levsin, and others), or propantheline (Pro-Banthine).



This list is not complete and other drugs may interact with guaifenesin and hydrocodone. 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 Condasin resources


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


  • CodiCLEAR DH Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

  • Entuss Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

  • Tusso-HC Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)



Compare Condasin with other medications


  • Cough


Where can I get more information?


  • Your pharmacist can provide more information about guaifenesin and hydrocodone.

See also: Condasin side effects (in more detail)


chlorambucil


Generic Name: chlorambucil (klor AM bue sil)

Brand Names: Leukeran


What is chlorambucil?

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


Chlorambucil is used to treat several types of cancer, including Hodgkin's disease and certain types of leukemia or lymphoma.


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


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


Do not use chlorambucil if you are pregnant. It could harm the unborn baby.

Taking chlorambucil may increase your risk of developing other types of cancer. Chlorambucil may also affect fertility (your ability to have children), whether you are a man or a woman. Ask your doctor about your individual risk.


Chlorambucil can lower blood cells that help your body fight infections. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Tell your doctor at once if you develop signs of infection.


Do not receive a "live" vaccine while you are being treated with chlorambucil, and for at least 3 months after your treatment ends. The vaccine may not work as well during this time, and may not fully protect you from disease. Stop taking chlorambucil and call your doctor at once if you have a seizure, red or peeling skin rash, severe nausea or stomach pain, jaundice (yellowing of your skin or eyes), fever, chills, sore throat, ongoing cough, flu symptoms, mouth sores, easy bruising or bleeding, or any unusual mass or lump.

What should I discuss with my healthcare provider before taking chlorambucil?


You should not use this medication if you are allergic to chlorambucil, or if you have received this medication in the past without successful treatment of your condition.

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



  • kidney disease;




  • liver disease;




  • a history of seizures;




  • a history of head injury or brain tumor; or




  • if you have received radiation or chemotherapy within the past 4 weeks.




FDA pregnancy category D. Do not use chlorambucil if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. This medication may affect fertility (your ability to have children), whether you are a man or a woman. It is not known whether chlorambucil passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking chlorambucil.

Taking chlorambucil may increase your risk of developing other types of cancer. Talk to your doctor about your specific risk.


How should I take chlorambucil?


You must remain under the care of a doctor while you are using chlorambucil.

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.


Chlorambucil is usually taken for 3 to 6 weeks. Follow your doctor's instructions.


Your doctor may occasionally change your dose to make sure you get the best results.


Chlorambucil can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Visit your doctor regularly.


Store chlorambucil tablets in the refrigerator, do not freeze.

See also: Chlorambucil dosage (in more detail)

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 agitation, loss of balance or coordination, or seizure (convulsions).


What should I avoid while taking chlorambucil?


Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.


Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth. Do not receive a "live" vaccine while you are being treated with chlorambucil, and for at least 3 months after your treatment ends. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), oral polio, rotavirus, typhoid, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.

Chlorambucil 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. Stop taking chlorambucil and call your doctor at once if you have a serious side effect such as:

  • seizure (convulsions);




  • fever, chills, body aches, flu symptoms, sores in your mouth and throat, ongoing cough;




  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;




  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;




  • fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;




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




  • an unusual mass or lump;




  • chest discomfort, dry cough or hack;




  • feeling short of breath on exertion;




  • feeling weak or tired, loss of appetite, rapid weight loss;




  • severe nausea, vomiting, or diarrhea; or




  • missed menstrual periods.



Less serious side effects:



  • mild nausea, vomiting, or diarrhea;




  • tremors or shaking; or




  • numbness, burning, pain, or tingly feeling.



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.


Chlorambucil Dosing Information


Usual Adult Dose for Hodgkin's Disease:

For initiation of therapy or for short courses of treatment:
Usual Dosage: 0.1 to 0.2 mg/kg orally daily for 3 to 6 weeks as required. (This usually amounts to 4 to 10 mg per day for the average patient.) The entire daily dose may be given at one time. The dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as there is an abrupt fall in the white blood cell count. Patients with Hodgkin's disease usually require 0.2 mg/kg daily. Patients with other lymphomas or chronic lymphocytic leukemia usually require only 0.1 mg/kg daily. When lymphocytic infiltration of the bone marrow is present, or when the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg (about 6 mg for the average patient).

Alternatively the initial dosage of chlorambucil for the treatment of Hodgkin's disease is 10 mg orally once a day for seven days out of twenty one. This regimen also includes vinblastine, procarbazine, prednisolone, etoposide, vincristine, and doxorubicin.

Alternate schedules for the treatment of chronic lymphocytic leukemia employing intermittent, biweekly, or once-monthly pulse doses of chlorambucil have been reported. Intermittent schedules of chlorambucil begin with an initial single dose of 0.4 mg/kg. Doses are generally increased by 0.1 mg/kg until control of lymphocytosis or toxicity is observed. Subsequent doses are modified to produce mild hematologic toxicity. It is felt that the response rate of chronic lymphocytic leukemia to the biweekly or once-monthly schedule of chlorambucil administration is similar or better to that previously reported with daily administration and that hematologic toxicity was less than or equal to that encountered in studies using daily chlorambucil.

Radiation and cytotoxic drugs render the bone marrow more vulnerable to damage, and chlorambucil should be used with particular caution within 4 weeks of a full course of radiation therapy or chemotherapy. However, small doses of palliative radiation over isolated foci remote from the bone marrow will not usually depress the neutrophil and platelet count. In these cases chlorambucil may be given in the customary dosage.

It is presently felt that short courses of treatment are safer than continuous maintenance therapy, although both methods have been effective. It must be recognized that continuous therapy may give the appearance of "maintenance" in patients who are actually in remission and have no immediate need for further drug. If maintenance dosage is used, it should not exceed 0.1 mg/kg daily and may well be as low as 0.03 mg/kg daily.

Typical maintenance dose is 2 mg to 4 mg daily, or less, depending on the status of the blood counts. It may, therefore, be desirable to withdraw the drug after maximal control has been achieved, since intermittent therapy reinstituted at time of relapse may be as effective as continuous treatment.

Usual Adult Dose for Chronic Lymphocytic Leukemia:

For initiation of therapy or for short courses of treatment:
Usual Dosage: 0.1 to 0.2 mg/kg orally daily for 3 to 6 weeks as required. (This usually amounts to 4 to 10 mg per day for the average patient.) The entire daily dose may be given at one time. The dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as there is an abrupt fall in the white blood cell count. Patients with Hodgkin's disease usually require 0.2 mg/kg daily. Patients with other lymphomas or chronic lymphocytic leukemia usually require only 0.1 mg/kg daily. When lymphocytic infiltration of the bone marrow is present, or when the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg (about 6 mg for the average patient).

Alternatively the initial dosage of chlorambucil for the treatment of Hodgkin's disease is 10 mg orally once a day for seven days out of twenty one. This regimen also includes vinblastine, procarbazine, prednisolone, etoposide, vincristine, and doxorubicin.

Alternate schedules for the treatment of chronic lymphocytic leukemia employing intermittent, biweekly, or once-monthly pulse doses of chlorambucil have been reported. Intermittent schedules of chlorambucil begin with an initial single dose of 0.4 mg/kg. Doses are generally increased by 0.1 mg/kg until control of lymphocytosis or toxicity is observed. Subsequent doses are modified to produce mild hematologic toxicity. It is felt that the response rate of chronic lymphocytic leukemia to the biweekly or once-monthly schedule of chlorambucil administration is similar or better to that previously reported with daily administration and that hematologic toxicity was less than or equal to that encountered in studies using daily chlorambucil.

Radiation and cytotoxic drugs render the bone marrow more vulnerable to damage, and chlorambucil should be used with particular caution within 4 weeks of a full course of radiation therapy or chemotherapy. However, small doses of palliative radiation over isolated foci remote from the bone marrow will not usually depress the neutrophil and platelet count. In these cases chlorambucil may be given in the customary dosage.

It is presently felt that short courses of treatment are safer than continuous maintenance therapy, although both methods have been effective. It must be recognized that continuous therapy may give the appearance of "maintenance" in patients who are actually in remission and have no immediate need for further drug. If maintenance dosage is used, it should not exceed 0.1 mg/kg daily and may well be as low as 0.03 mg/kg daily.

Typical maintenance dose is 2 mg to 4 mg daily, or less, depending on the status of the blood counts. It may, therefore, be desirable to withdraw the drug after maximal control has been achieved, since intermittent therapy reinstituted at time of relapse may be as effective as continuous treatment.

Usual Adult Dose for Lymphoma:

For initiation of therapy or for short courses of treatment:
Usual Dosage: 0.1 to 0.2 mg/kg orally daily for 3 to 6 weeks as required. (This usually amounts to 4 to 10 mg per day for the average patient.) The entire daily dose may be given at one time. The dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as there is an abrupt fall in the white blood cell count. Patients with Hodgkin's disease usually require 0.2 mg/kg daily. Patients with other lymphomas or chronic lymphocytic leukemia usually require only 0.1 mg/kg daily. When lymphocytic infiltration of the bone marrow is present, or when the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg (about 6 mg for the average patient).

Alternatively the initial dosage of chlorambucil for the treatment of Hodgkin's disease is 10 mg orally once a day for seven days out of twenty one. This regimen also includes vinblastine, procarbazine, prednisolone, etoposide, vincristine, and doxorubicin.

Alternate schedules for the treatment of chronic lymphocytic leukemia employing intermittent, biweekly, or once-monthly pulse doses of chlorambucil have been reported. Intermittent schedules of chlorambucil begin with an initial single dose of 0.4 mg/kg. Doses are generally increased by 0.1 mg/kg until control of lymphocytosis or toxicity is observed. Subsequent doses are modified to produce mild hematologic toxicity. It is felt that the response rate of chronic lymphocytic leukemia to the biweekly or once-monthly schedule of chlorambucil administration is similar or better to that previously reported with daily administration and that hematologic toxicity was less than or equal to that encountered in studies using daily chlorambucil.

Radiation and cytotoxic drugs render the bone marrow more vulnerable to damage, and chlorambucil should be used with particular caution within 4 weeks of a full course of radiation therapy or chemotherapy. However, small doses of palliative radiation over isolated foci remote from the bone marrow will not usually depress the neutrophil and platelet count. In these cases chlorambucil may be given in the customary dosage.

It is presently felt that short courses of treatment are safer than continuous maintenance therapy, although both methods have been effective. It must be recognized that continuous therapy may give the appearance of "maintenance" in patients who are actually in remission and have no immediate need for further drug. If maintenance dosage is used, it should not exceed 0.1 mg/kg daily and may well be as low as 0.03 mg/kg daily.

Typical maintenance dose is 2 mg to 4 mg daily, or less, depending on the status of the blood counts. It may, therefore, be desirable to withdraw the drug after maximal control has been achieved, since intermittent therapy reinstituted at time of relapse may be as effective as continuous treatment.

Usual Pediatric Dose for Malignant Disease:

Remission Induction: 0.1 to 0.2 mg/kg/day or 4.5 mg/m2/day once daily for 3 to 6 weeks
Maintenance Therapy: 0.03 to 0.1 mg/kg/day

Nephrotic Syndrome: 0.1 to 0.2 mg/kg/day every day for 5 to 12 weeks with low dose prednisone.

Chronic Lymphocytic Leukemia:
Initial Dose: 0.4 mg/kg every 2 weeks. Increase dose by 0.1 mg/kg every 2 weeks until a response occurs and/or myelosuppression occurs.
Alternate Initial Dose: 0.4 mg/kg every 4 weeks. Increase dose by 0.2 mg/kg every 2 weeks until a response occurs and/or myelosuppression occurs.

Non-Hodgkin's Lymphoma: 0.1 mg/kg/day

Hodgkin's Lymphoma: 0.2 mg/kg/day


What other drugs will affect chlorambucil?


There may be other drugs that can interact with chlorambucil. 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 chlorambucil resources


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


  • chlorambucil Advanced Consumer (Micromedex) - Includes Dosage Information

  • Chlorambucil Professional Patient Advice (Wolters Kluwer)

  • Chlorambucil Monograph (AHFS DI)

  • Chlorambucil MedFacts Consumer Leaflet (Wolters Kluwer)

  • Leukeran Prescribing Information (FDA)



Compare chlorambucil with other medications


  • Cancer
  • Chronic Lymphocytic Leukemia
  • Hodgkin's Lymphoma
  • Lymphoma


Where can I get more information?


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

See also: chlorambucil side effects (in more detail)


Carbidopa and Levodopa




Dosage Form: tablet, extended release

Carbidopa and Levodopa Description


Carbidopa and Levodopa extended-release tablets are for the treatment of Parkinson's disease and syndrome.


Carbidopa, USP, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.25. It is designated chemically as(-)-L-alpha-hydrazino-alpha-methyl-beta-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its structural formula is:



Tablet content is expressed in terms of anhydrous carbidopa, which has a molecular weight of 226.23.


Levodopa, USP, an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.19. It is designated chemically as (-)-L-alpha-amino- beta-(3,4-dihydroxybenzene) propanoic acid. Its structural formula is:



Each extended-release tablet, for oral administration, contains either 25 mg of carbidopa and 100 mg of levodopa or 50 mg of carbidopa and 200 mg of levodopa. In addition, each tablet contains the following inactive ingredients: FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, hydroxypropyl cellulose, hypromellose, and magnesium stearate.


Carbidopa and Levodopa extended-release tablets are designed in a drug delivery system that controls the release of Carbidopa and Levodopa as the tablets slowly erode. The 25 mg/100 mg Carbidopa and Levodopa extended-release tablet is available to facilitate titration and as an alternative to the half-tablet of 50 mg/200 mg Carbidopa and Levodopa extended-release.



Carbidopa and Levodopa - Clinical Pharmacology



Mechanism of Action


Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Symptomatic treatments, such as levodopa therapies, may permit the patient better mobility.


Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier. However, levodopa, the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease.



Pharmacodynamics


When levodopa is administered orally it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. For this reason, large doses of levodopa are required for adequate therapeutic effect and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues.


Since levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients on a high protein diet.


Carbidopa inhibits decarboxylation of peripheral levodopa. It does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system.


Since its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain.


Patients treated with levodopa therapy for Parkinson's disease may develop motor fluctuations characterized by end-of-dose failure, peak dose dyskinesia, and akinesia. The advanced form of motor fluctuations (‘on-off’ phenomenon) is characterized by unpredictable swings from mobility to immobility. Although the causes of the motor fluctuations are not completely understood, in some patients they may be attenuated by treatment regimens that produce steady plasma levels of levodopa.


Carbidopa and Levodopa extended-release tablets contain either 25 mg of carbidopa and 100 mg of levodopa or 50 mg of carbidopa and 200 mg of levodopa, in a sustained-release dosage form designed to release these ingredients over a 4 to 6 hour period. With Carbidopa and Levodopa extended-release there is less variation in plasma levodopa levels than with Carbidopa and Levodopa immediate-release, the conventional formulation. However, Carbidopa and Levodopa extended-release is less systemically bioavailable than Carbidopa and Levodopa immediate-release and may require increased daily doses to achieve the same level of symptomatic relief as provided by Carbidopa and Levodopa immediate-release.


In clinical trials, patients with moderate to severe motor fluctuations who received Carbidopa and Levodopa extended-release did not experience quantitatively significant reductions in ‘off’ time when compared to Carbidopa and Levodopa immediate-release. However, global ratings of improvement as assessed by both patient and physician were better during therapy with Carbidopa and Levodopa extended-release than with Carbidopa and Levodopa immediate-release. In patients without motor fluctuations, Carbidopa and Levodopa extended-release under controlled conditions, provided the same therapeutic benefit with less frequent dosing when compared to Carbidopa and Levodopa immediate-release.



Pharmacokinetics


Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.


Elimination half-life of levodopa in the presence of carbidopa is about 1.5 hours. Following Carbidopa and Levodopa extended-release, the apparent half-life of levodopa may be prolonged because of continuous absorption.


In healthy elderly subjects (56 to 67 years old) the mean time-to-peak concentration of levodopa after a single dose of 50 mg/200 mg Carbidopa and Levodopa extended-release was about 2 hours as compared to 0.5 hours after standard Carbidopa and Levodopa immediate-release. The maximum concentration of levodopa after a single dose of Carbidopa and Levodopa extended-release was about 35% of the standard Carbidopa and Levodopa immediate-release (1151 vs. 3256 ng/mL). The extent of availability of levodopa from Carbidopa and Levodopa extended-release was about 70% to 75% relative to intravenous levodopa or standard Carbidopa and Levodopa immediate-release in the elderly. The absolute bioavailability of levodopa from Carbidopa and Levodopa extended-release (relative to I.V.) in young subjects was shown to be only about 44%. The extent of availability and the peak concentrations of levodopa were comparable in the elderly after a single dose and at steady-state after t.i.d. administration of 50 mg/200 mg Carbidopa and Levodopa extended-release. In elderly subjects, the average trough levels of levodopa at steady-state after the extended-release tablet were about 2-fold higher than after the standard Carbidopa and Levodopa immediate-release (163 vs. 74 ng/mL).


In these studies, using similar total daily doses of levodopa, plasma levodopa concentrations with Carbidopa and Levodopa extended-release fluctuated in a narrower range than with Carbidopa and Levodopa immediate-release. Because the bioavailability of levodopa from Carbidopa and Levodopa extended-release relative to Carbidopa and Levodopa immediate-release is approximately 70% to 75%, the daily dosage of levodopa necessary to produce a given clinical response with the extended-release formulation will usually be higher.


The extent of availability and peak concentrations of levodopa after a single dose of 50 mg/200 mg Carbidopa and Levodopa extended-release increased by about 50% and 25%, respectively, when administered with food.


At steady-state, the bioavailability of carbidopa from Carbidopa and Levodopa immediate-release tablets is approximately 99% relative to the concomitant administration of Carbidopa and Levodopa. At steady-state, carbidopa bioavailability from 50 mg/200 mg Carbidopa and Levodopa extended-release is approximately 58% relative to that from Carbidopa and Levodopa immediate-release.


Pyridoxine hydrochloride (vitamin B6), in oral doses of 10 mg to 25 mg, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine.



Indications and Usage for Carbidopa and Levodopa


Carbidopa and Levodopa extended-release tablets are indicated in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.



Contraindications


Nonselective MAO inhibitors are contraindicated for use with Carbidopa and Levodopa extended-release tablets. These inhibitors must be discontinued at least 2 weeks prior to initiating therapy with Carbidopa and Levodopa extended-release. Carbidopa and Levodopa extended-release may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline hydrochloride) (see PRECAUTIONS: Drug Interactions).


Carbidopa and Levodopa extended-release is contraindicated in patients with known hypersensitivity to any component of this drug and in patients with narrow-angle glaucoma.


Because levodopa may activate a malignant melanoma, Carbidopa and Levodopa extended-release should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.



Warnings


When patients are receiving levodopa without a decarboxylase inhibitor, levodopa must be discontinued at least 12 hours before Carbidopa and Levodopa extended-release is started. In order to reduce adverse reactions, it is necessary to individualize therapy. Carbidopa and Levodopa extended-release should be substituted at a dosage that will provide approximately 25% of the previous levodopa dosage (see DOSAGE AND ADMINISTRATION).


Carbidopa does not decrease adverse reactions due to central effects of levodopa. By permitting more levodopa to reach the brain, particularly when nausea and vomiting is not a dose-limiting factor, certain adverse CNS effects, e.g., dyskinesias, will occur at lower dosages and sooner during therapy with Carbidopa and Levodopa extended-release than with levodopa alone.


Patients receiving Carbidopa and Levodopa extended-release may develop increased dyskinesias compared to Carbidopa and Levodopa immediate-release. Dyskinesias are a common side effect of carbidopa-levodopa treatment. The occurrence of dyskinesias may require dosage reduction.


As with levodopa, Carbidopa and Levodopa extended-release may cause mental disturbances. These reactions are thought to be due to increased brain dopamine following administration of levodopa. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution.


Carbidopa and Levodopa extended-release should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.


As with levodopa, care should be exercised in administering Carbidopa and Levodopa extended-release to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care.


As with levodopa, treatment with Carbidopa and Levodopa extended-release may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.



Neuroleptic Malignant Syndrome (NMS)


Sporadic cases of a symptom complex resembling NMS have been reported in association with dose reductions or withdrawal of Carbidopa and Levodopa immediate-release and Carbidopa and Levodopa extended-release.


Therefore, patients should be observed carefully when the dosage of Carbidopa and Levodopa extended-release is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.


NMS is an uncommon but life threatening syndrome characterized by fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper- or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin have been reported.


The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.


The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of NMS; however, their effectiveness has not been demonstrated in controlled studies.



Precautions



General


As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy.


Patients with chronic wide-angle glaucoma may be treated cautiously with Carbidopa and Levodopa extended-release provided the intraocular pressure is well controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.


Dopaminergic agents, including levodopa, may be associated with somnolence and very rarely episodes of sudden onset of sleep. In some cases, these episodes may occur without awareness or warning during daily activities. Patients must be informed of this and advised to exercise caution while driving or operating machines while being treated with dopaminergic agents, including levodopa. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines (see Information for Patients).



Melanoma


Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear.


For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using Carbidopa and Levodopa extended-release for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).



Information for Patients


The patient should be informed that Carbidopa and Levodopa extended-release tablets are a sustained-release formulation of Carbidopa and Levodopa which releases these ingredients over a 4 to 6 hour period. It is important that Carbidopa and Levodopa extended-release be taken at regular intervals according to the schedule outlined by the physician. The patient should be cautioned not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other Carbidopa and Levodopa preparations, without first consulting the physician.


If abnormal involuntary movements appear or get worse during treatment with Carbidopa and Levodopa extended-release, the physician should be notified, as dosage adjustment may be necessary.


Patients should be advised that sometimes the onset of effect of the first morning dose of Carbidopa and Levodopa extended-release may be delayed for up to one hour compared with the response usually obtained from the first morning dose of Carbidopa and Levodopa immediate-release. The physician should be notified if such delayed responses pose a problem in treatment.


Patients should be advised that, occasionally, dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of Carbidopa and Levodopa extended-release. Although the color appears to be clinically insignificant, garments may become discolored.


The patient should be informed that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multi-vitamin tablets) may also reduce the amount of levodopa available to the body. The above factors may reduce the clinical effectiveness of the levodopa or carbidopa-levodopa therapy.


Patients must be advised that the whole or half tablet should be swallowed without chewing or crushing.


Patients should be alerted to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. Patients should be advised to exercise caution while driving or operating machinery and that if they have experienced somnolence and/or sudden sleep onset, they must refrain from these activities (see PRECAUTIONS: General).


There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease, including Carbidopa and Levodopa extended-release. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with Carbidopa and Levodopa extended-release. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while taking Carbidopa and Levodopa extended-release. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking Carbidopa and Levodopa extended-release.


NOTE: The suggested advice to patients being treated with Carbidopa and Levodopa extended-release tablets is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.



Laboratory Tests


Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase, and bilirubin. Abnormalities in blood urea nitrogen and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of Carbidopa and Levodopa preparations than with levodopa.


Carbidopa and Levodopa preparations, such as Carbidopa and Levodopa immediate-release and Carbidopa and Levodopa extended-release, may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose-oxidase methods of testing for glucosuria.


Cases of falsely diagnosed pheochromocytoma in patients on carbidopa-levodopa therapy have been reported very rarely. Caution should be exercised when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on levodopa or carbidopa-levodopa therapy.



Drug Interactions


Caution should be exercised when the following drugs are administered concomitantly with Carbidopa and Levodopa extended-release.


Symptomatic postural hypotension has occurred when Carbidopa and Levodopa preparations were added to the treatment of patients receiving some antihypertensive drugs. Therefore, when therapy with Carbidopa and Levodopa extended-release is started, dosage adjustment of the antihypertensive drug may be required.


For patients receiving monoamine oxidase (MAO) inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone (see CONTRAINDICATIONS).


There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and Carbidopa and Levodopa preparations.


Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with Carbidopa and Levodopa extended-release should be carefully observed for loss of therapeutic response.


Iron salts may reduce the bioavailability of levodopa and carbidopa. The clinical relevance is unclear.


Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.



Carcinogenesis, Mutagenesis, Impairment of Fertility


In a 2-year bioassay of Carbidopa and Levodopa immediate-release, no evidence of carcinogenicity was found in rats receiving doses of approximately 2 times the maximum daily human dose of carbidopa and 4 times the maximum daily human dose of levodopa (equivalent to 8 Carbidopa and Levodopa extended-release tablets).


In reproduction studies with Carbidopa and Levodopa immediate-release, no effects on fertility were found in rats receiving doses of approximately 2 times the maximum daily human dose of carbidopa and 4 times the maximum daily human dose of levodopa (equivalent to 8 Carbidopa and Levodopa extended-release tablets).



Pregnancy


Teratogenic Effects Pregnancy Category C

No teratogenic effects were observed in a study in mice receiving up to 20 times the maximum recommended human dose of Carbidopa and Levodopa immediate-release. There was a decrease in the number of live pups delivered by rats receiving approximately 2 times the maximum recommended human dose of carbidopa and approximately 5 times the maximum recommended human dose of levodopa during organogenesis. Carbidopa and Levodopa immediate-release caused both visceral and skeletal malformations in rabbits at all doses and ratios of carbidopa/levodopa tested, which ranged from 10 times/5 times the maximum recommended human dose of carbidopa/levodopa to 20 times/10 times the maximum recommended human dose of carbidopa/levodopa.


There are no adequate or well controlled studies in pregnant women. It has been reported from individual cases that levodopa crosses the human placental barrier, enters the fetus, and is metabolized. Carbidopa concentrations in fetal tissue appeared to be minimal. Use of Carbidopa and Levodopa extended-release in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to mother and child.



Nursing Mothers


In a study of one nursing mother with Parkinson’s disease, excretion of levodopa in human breast milk was reported. Therefore, caution should be exercised when Carbidopa and Levodopa extended-release is administered to a nursing woman.



Pediatric Use


Safety and effectiveness in pediatric patients have not been established. Use of the drug in patients below the age of 18 is not recommended.



Adverse Reactions


In controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on Carbidopa and Levodopa immediate-release were randomized to therapy with either Carbidopa and Levodopa immediate-release or Carbidopa and Levodopa extended-release. The adverse experience frequency profile of Carbidopa and Levodopa extended-release did not differ substantially from that of Carbidopa and Levodopa immediate-release, as shown in Table 1.
























































































Table 1 Clinical Adverse Experiences Occurring In 1% or Greater of Patients
Adverse

Experience
Carbidopa

and

Levodopa

Extended-release

n=491

%
Carbidopa

and

Levodopa

Immediate-release

n=524

%
Dyskinesia16.512.2
Nausea5.55.7
Hallucinations3.93.2
Confusion3.72.3
Dizziness2.92.3
Depression2.21.3
Urinary tract infection2.22.3
Headache21.9
Dream abnormalities1.80.8
Dystonia1.80.8
Vomiting1.81.9
Upper respiratory infection1.81
Dyspnea1.60.4
‘On-Off’ phenomena1.61.1
Back pain1.60.6
Dry mouth1.41.1
Anorexia1.21.1
Diarrhea1.20.6
Insomnia1.21
Orthostatic hypotension11.1
Shoulder pain10.6
Chest pain10.8
Muscle cramps0.81
Paresthesia0.81.1
Urinary frequency0.81.1
Dyspepsia0.61.1
Constipation0.21.5

Abnormal laboratory findings occurring at a frequency of 1% or greater in approximately 443 patients who received Carbidopa and Levodopa extended-release and 475 who received Carbidopa and Levodopa immediate-release during controlled clinical trials included: decreased hemoglobin and hematocrit; elevated serum glucose; white blood cells, bacteria and blood in the urine.


The adverse experiences observed in patients in uncontrolled studies were similar to those seen in controlled clinical studies.


Other adverse experiences reported overall in clinical trials in 748 patients treated with Carbidopa and Levodopa extended-release, listed by body system in order of decreasing frequency, include:


Body as a Whole: Asthenia, fatigue, abdominal pain, orthostatic effects.


Cardiovascular: Palpitation, hypertension, hypotension, myocardial infarction.


Gastrointestinal: Gastrointestinal pain, dysphagia, heartburn.


Metabolic: Weight loss.


Musculoskeletal: Leg pain.


Nervous System/Psychiatric: Chorea, somnolence, falling, anxiety, disorientation, decreased mental acuity, gait abnormalities, extrapyramidal disorder, agitation, nervousness, sleep disorders, memory impairment.


Respiratory: Cough, pharyngeal pain, common cold.


Skin: Rash.


Special Senses: Blurred vision.


Urogenital: Urinary incontinence.


Laboratory Tests: Decreased white blood cell count and serum potassium; increased BUN, serum creatinine and serum LDH; protein and glucose in the urine.


The following adverse experiences have been reported in post-marketing experience with Carbidopa and Levodopa extended-release:


Cardiovascular: Cardiac irregularities, syncope.


Gastrointestinal: Taste alterations, dark saliva.


Hypersensitivity: Angioedema, urticaria, pruritus, bullous lesions (including pemphigus-like reactions).


Nervous System/Psychiatric: Neuroleptic malignant syndrome (NMS), (see WARNINGS), increased tremor, peripheral neuropathy, psychotic episodes including delusions and paranoid ideation, pathological gambling, increased libido including hypersexuality, impulse control symptoms.


Skin: Alopecia, flushing, dark sweat.


Urogenital: Dark urine.


Other adverse reactions that have been reported with levodopa alone and with various carbidopa-levodopa formulations and may occur with Carbidopa and Levodopa extended-release are:


Cardiovascular: Phlebitis.


Gastrointestinal: Gastrointestinal bleeding, development of duodenal ulcer, sialorrhea, bruxism, hiccups, flatulence, burning sensation of tongue.


Hematologic: Hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.


Hypersensitivity: Henoch-Schonlein purpura.


Metabolic: Weight gain, edema.


Nervous System/Psychiatric: Ataxia, depression with suicidal tendencies, dementia, euphoria, convulsions (however, a causal relationship has not been established); bradykinetic episodes, numbness, muscle twitching, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, activation of latent Horner's syndrome, nightmares.


Skin: Malignant melanoma (see also CONTRAINDICATIONS), increased sweating.


Special Senses: Oculogyric crisis, mydriasis, diplopia.


Urogenital: Urinary retention, priapism.


Miscellaneous: Faintness, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns.


Laboratory Tests: Abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), bilirubin, Coombs test, uric acid.



Overdosage


Management of acute overdosage with Carbidopa and Levodopa extended-release is the same as with levodopa. Pyridoxine is not effective in reversing the actions of Carbidopa and Levodopa extended-release.


General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered judiciously and an adequate airway maintained. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as Carbidopa and Levodopa extended-release should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known.


Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500 to 2000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3360 mg/kg.



Carbidopa and Levodopa Dosage and Administration


Carbidopa and Levodopa extended-release tablets contain Carbidopa and Levodopa in a 1:4 ratio as either the 50 mg/200 mg tablet or the 25 mg/100 mg tablet. The daily dosage of Carbidopa and Levodopa extended-release tablets must be determined by careful titration. Patients should be monitored closely during the dose adjustment period, particularly with regard to appearance or worsening of involuntary movements, dyskinesias or nausea. Carbidopa and Levodopa extended-release tablets should not be chewed or crushed.


Standard drugs for Parkinson’s disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while Carbidopa and Levodopa extended-release tablets are being administered, although their dosage may have to be adjusted.


Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, Carbidopa and Levodopa extended-release tablets can be given to patients receiving supplemental pyridoxine (vitamin B6).



Initial Dosage


Patients Currently Treated with Conventional Carbidopa-Levodopa Preparations

Studies show that peripheral dopa-decarboxylase is saturated by the bioavailable carbidopa at doses of 70 mg a day and greater. Because the bioavailabilities of Carbidopa and Levodopa in Carbidopa and Levodopa immediate-release tablets and Carbidopa and Levodopa extended-release tablets are different, appropriate adjustments should be made, as shown in Table 2.

















Table 2 Approximate Bioavailabilities at Steady-State*

*

This table is only a guide to bioavailabilities since other factors such as food, drugs, and inter-patient variabilities may affect the bioavailability of Carbidopa and Levodopa.


The extent of availability of levodopa from Carbidopa and Levodopa extended-release tablets was about 70% to 75% relative to intravenous levodopa or standard Carbidopa and Levodopa immediate-release tablets in the elderly.


The extent of availability of levodopa from Carbidopa and Levodopa immediate-release tablets was 99% relative to intravenous levodopa in the healthy elderly.

TabletAmount of Levodopa

(mg) in Each Tablet
Approximate

Bioavailability
Approximate Amount

of Bioavailable Levodopa

(mg) in Each Tablet
Carbidopa and Levodopa

Extended-release Tablets

50 mg/200 mg
2000.70 to 0.75140 to 150
Carbidopa and Levodopa

Immediate-release Tablets

25 mg/100 mg
1000.9999

Dosage with Carbidopa and Levodopa extended-release tablets should be substituted at an amount that provides approximately 10% more levodopa per day, although this may need to be increased to a dosage that provides up to 30% more levodopa per day depending on clinical response (see DOSAGE AND ADMINISTRATION: Titration with Carbidopa and Levodopa Extended-release Tablets). The interval between doses of Carbidopa and Levodopa extended-release tablets should be 4 to 8 hours during the waking day (see CLINICAL PHARMACOLOGY: Pharmacodynamics).


A guideline for initiation of Carbidopa and Levodopa extended-release tablets is shown in Table 3.

















Table 3 Guidelines for Initial Conversion from Carbidopa and Levodopa Immediate-release to Carbidopa and Levodopa Extended-release Tablets

*

For dosing ranges not shown in the table see DOSAGE AND ADMINISTRATION: Initial Dosage: Patients Currently Treated with Conventional Carbidopa and Levodopa Preparations.

Carbidopa and Levodopa Immediate-release TabletsCarbidopa and Levodopa Extended-release Tablets
Total Daily Dose* Levodopa (mg)Suggested Dosage Regimen
300–400200 mg b.i.d.
500–600300 mg b.i.d. or

200 mg t.i.d.
700–800A total of 800 mg in 3 or more divided doses (e.g., 300 mg a.m., 300 mg early p.m. and 200 mg later p.m.)
900–1000A total of 1000 mg in 3 or more divided doses (e.g., 400 mg a.m., 400 mg early p.m., and 200 mg later p.m.)
Patients Currently Treated with Levodopa Without a Decarboxylase Inhibitor

Levodopa must be discontinued at least 12 hours before therapy with Carbidopa and Levodopa extended-release tablets is started. Carbidopa and Levodopa extended-release tablets should be substituted at a dosage that will provide approximately 25% of the previous levodopa dosage. In patients with mild to moderate disease, the initial dose is usually one tablet of 50 mg/200 mg Carbidopa and Levodopa extended-release tablets b.i.d.


Patients Not Receiving Levodopa

In patients with mild to moderate disease, the initial recommended dose is one tablet of 50 mg/200 mg Carbidopa and Levodopa extended-release tablets b.i.d. Initial dosage should not be given at intervals of less than 6 hours.


Titration with Carbidopa and Levodopa Extended-release Tablets

Following initiation of therapy, doses and dosing intervals may be increased or decreased depending upon therapeutic response. Most patients have been adequately treated with doses of Carbidopa and Levodopa extended-release tablets that provide 400 mg to 1600 mg of levodopa per day, administered as divided doses at intervals ranging from 4 to 8 hours during the waking day. Higher doses of Carbidopa and Levodopa extended-release tablets (2400 mg or more of levodopa per day) and shorter intervals (less than 4 hours) have been used, but are not usually recommended.


When doses of Carbidopa and Levodopa extended-release tablets are given at intervals of less than 4 hours, and/or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day.


An interval of at least 3 days between dosage adjustments is recommended.



Maintenance


Because Parkinson's disease is progressive, periodic clinical evaluations are recommended; adjustment of the dosage regimen of Carbidopa and Levodopa extended-release tablets may be required.



Addition of Other Antiparkinson Medications


Anticholinergic agents, dopamine agonists, and amantadine can be given with Carbidopa and Levodopa extended-release tablets. Dosage adjustment of Carbidopa and Levodopa extended-release tablets may be necessary when these agents are added.


A dose of Carbidopa and Levodopa immediate-release tablets 25 mg/100 mg or 10 mg/100 mg (one half or a whole tablet) can be added to the dosage regimen of Carbidopa and Levodopa extended-release tablets in selected patients with advanced disease who need additional immediate-release levodopa for a brief time during daytime hours.



Interruption of Therapy


Sporadic cases of a symptom complex resembling Neuroleptic Malignant Syndrome (NMS) have been associated with dose reductions and withdrawal of Carbidopa and Levodopa immediate-release tablets or Carbidopa and Levodopa extended-release tablets.


Patients should be observed carefully if abrupt reduction or discontinuation of Carbidopa and Levodopa extended-release tablets is required, especially if the patient is receiving neuroleptics (see WAR