carbetapentane, phenylephrine, and pyrilamine

Generic Name: carbetapentane, phenylephrine, and pyrilamine (kar BET a PEN tane, FEN il EFF rin, and pir IL a meen)

Brand Names: C-Tanna 12D, Tannate 12D S, Tannihist-12D, Tussi-12D, Tussi-12D S

What is carbetapentane, phenylephrine, and pyrilamine?

Carbetapentane is a cough suppressant.

Pyrilamine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of carbetapentane, phenylephrine, and pyrilamine is used to treat runny or stuffy nose, sinus congestion, and cough caused by allergies, the common cold, or flu.

Carbetapentane, phenylephrine, and pyrilamine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about carbetapentane, phenylephrine, and pyrilamine?

Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Tell your doctor about all your medical conditions before you take this carbetapentane, phenylephrine, and pyrilamine.

Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Avoid drinking alcohol while you are taking this medication.

Do not use any other over-the-counter cough, cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains an antihistamine, decongestant, or cough suppressant.

What should I discuss with my healthcare provider before taking carbetapentane, phenylephrine, and pyrilamine?

You should not use this medication if you are allergic to carbetapentane, phenylephrine, or pyrilamine, or to other decongestants or antihistamines. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Before using this medication, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  heart disease, high blood pressure, or a heart rhythm disorder;

  
  


• 
  

  asthma, emphysema, or chronic obstructive pulmonary disease (COPD);

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  diabetes;

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  glaucoma;

  
  


• 
  

  kidney disease;

  
  


• 
  

  gallbladder disease;

  
  


• 
  

  Addison's disease;

  
  


• 
  

  a stomach ulcer or obstruction;

  
  


• 
  

  an enlarged prostate; or

  
  


• 
  

  problems with urination.

  
  

If you have any of these conditions, you may not be able to take carbetapentane, phenylephrine, and pyrilamine, or you may need a dose adjustment or special tests during treatment.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. This medication may pass into breast milk and could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take carbetapentane, phenylephrine, and pyrilamine?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Always ask a doctor before giving cough or cold medicine to a child. Death can occur from the misuse of cough or cold medicine in very young children. Shake the oral suspension (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

This medication can cause you to have unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash. Store the medicine at room temperature away from moisture and heat.

See also: Carbetapentane, phenylephrine, and pyrilamine dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking carbetapentane, phenylephrine, and pyrilamine?

Avoid drinking alcohol while you are taking this medicine. Do not use any other over-the-counter cough, cold, allergy, pain, or sleeping medication without first asking your doctor or pharmacist. Decongestants, antihistamines, and cough suppressants are contained in many medicines available over the counter. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains a decongestant, antihistamine, or cough suppressant.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid using other medicines that make you sleepy (such as pain medication, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety). They can add to sleepiness caused by carbetapentane, phenylephrine, and pyrilamine.

Carbetapentane, phenylephrine, and pyrilamine 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 any of these serious side effects:

• 
  

  fast, pounding, or uneven heartbeat;

  
  


• 
  

  slow, shallow breathing;

  
  


• 
  

  confusion, hallucinations, unusual thoughts or behavior;

  
  


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  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


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  urinating less than usual or not at all;

  
  


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  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

  
  


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  increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure); or

  
  


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  jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

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  dizziness, drowsiness, blurred vision;

  
  


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  dry mouth, nose, or eyes;

  
  


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  nausea, stomach pain, constipation, loss of appetite;

  
  


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  warmth, tingling, or redness under your skin;

  
  


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  problems with memory or concentration;

  
  


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  ringing in your ears;

  
  


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  feeling excited or restless; or

  
  


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  sleep problems (insomnia).

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Carbetapentane, phenylephrine, and pyrilamine Dosing Information

Usual Adult Dose for Cough and Nasal Congestion:

carbetapentane/phenylephrine/pyrilamine 30 mg-5 mg-30 mg/5 mL oral suspension:
5 to 10 mL orally every 12 hours

carbetapentane/phenylephrine/pyrilamine 60 mg-10 mg-40 mg oral tablet:
1 to 2 tablets orally every 12 hours

Usual Pediatric Dose for Cough and Nasal Congestion:

carbetapentane/phenylephrine/pyrilamine 30 mg-5 mg-30 mg/5 mL oral suspension:
2 to 6 yrs: 2.5 to 5 mL orally every 12 hours
>6 yrs: 5 to 10 mL orally every 12 hours

carbetapentane/phenylephrine/pyrilamine 60 mg-10 mg-40 mg oral tablet:
6 to 11 yrs: 1 to 2 tablets orally every 12 hours
>11 yrs: 1/2 to 1 tablet orally every 12 hours

What other drugs will affect carbetapentane, phenylephrine, and pyrilamine?

The following drugs can interact with carbetapentane, phenylephrine, and pyrilamine. Tell your doctor if you are using any of these:

• 
  

  celecoxib (Celebrex);

  
  


• 
  

  cinacalcet (Sensipar);

  
  


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  imatinib (Gleevec);

  
  


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  quinidine (Quinaglute, Quinidex);

  
  


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  ranolazine (Ranexa)

  
  


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  ritonavir (Norvir);

  
  


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  sibutramine (Meridia);

  
  


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  terbinafine (Lamisil);

  
  


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  an antidepressant;

  
  


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  a diuretic (water pill);

  
  


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  medicines to treat high blood pressure;

  
  


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  medication to treat irritable bowel syndrome;

  
  


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  bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol); or

  
  


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  aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others).

  
  

This list is not complete and there may be other drugs that can interact with carbetapentane, phenylephrine, and pyrilamine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More carbetapentane, phenylephrine, and pyrilamine resources

• Carbetapentane, phenylephrine, and pyrilamine Side Effects (in more detail)
• Carbetapentane, phenylephrine, and pyrilamine Dosage
• Carbetapentane, phenylephrine, and pyrilamine Use in Pregnancy & Breastfeeding
• Carbetapentane, phenylephrine, and pyrilamine Drug Interactions
• Carbetapentane, phenylephrine, and pyrilamine Support Group
• 0 Reviews for Carbetapentane, phenylephrine, and pyrilamine - Add your own review/rating

Compare carbetapentane, phenylephrine, and pyrilamine with other medications

• Cough and Nasal Congestion

Where can I get more information?

• Your pharmacist can provide more information about carbetapentane, phenylephrine, and pyrilamine.

See also: carbetapentane, phenylephrine, and pyrilamine side effects (in more detail)

ziconotide

Generic Name: ziconotide (zye KON oh tide)

Brand Names: Prialt

What is ziconotide?

Ziconotide is a non-narcotic pain reliever that works by blocking pain signals from the nerves to the brain.

Ziconotide is used to treat severe chronic pain in people who cannot use or do not respond to standard pain-relieving medications.

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

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

Severe psychiatric symptoms and neurological impairment may occur during treatment with ziconotide. You should not receive ziconotide if you have a history of psychiatric illness or psychotic event.

You should not use this medication if you are allergic to ziconotide, or if you have an uncontrolled bleeding or blood clotting disorder.

Ziconotide must be given only as an intrathecal injection through an infusion pump and should not be injected directly into a vein or other part of the body. Your doctor, nurse, or other healthcare provider will give you this injection.

Your doctor may occasionally change your dose or infusion pump flow rate to make sure you get the best results from this medication.

Tell your doctor if the medicine seems to stop working as well in relieving your pain. Tell your doctor if you regularly use other medicines that make you sleepy. Ziconotide can add to sleepiness caused by these other medications.

Call your doctor at once if you have a serious side effect, especially fever, neck stiffness, seizure (convulsions), extreme drowsiness or tired feeling, confusion, disorientation, hallucinations, thoughts of hurting yourself, or decreased consciousness.

What should I discuss with my healthcare provider before using ziconotide?

Severe psychiatric symptoms and neurological impairment may occur during treatment with ziconotide. You should not receive ziconotide if you have a history of psychiatric illness or psychotic event.

You should not use this medication if you are allergic to ziconotide, or if you have an uncontrolled bleeding or blood clotting disorder.

FDA pregnancy category C. It is not known whether ziconotide is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether ziconotide passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use ziconotide?

Ziconotide is given as an injection into the space around your spinal cord (intrathecal injection) using a computerized, portable infusion pump to control the rate of medication you receive. You may need to use this medication for a period of many years.

Ziconotide must be given only as an intrathecal injection through an infusion pump and should not be injected directly into a vein or other part of the body. Your doctor, nurse, or other healthcare provider will give you this injection.

Your doctor may occasionally change your dose or infusion pump flow rate to make sure you get the best results from this medication.

Tell your doctor if the medicine seems to stop working as well in relieving your pain.

To be sure ziconotide is helping your condition and not causing harmful effects, your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

If you also use a narcotic pain medication, do not stop using it suddenly or you may have unpleasant withdrawal symptoms. Talk with your doctor about using less and less of the narcotic medication before stopping completely.

What happens if I miss a dose?

Since ziconotide dosing and infusion pump programming is administered by a healthcare professional, you are not likely to miss a dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine or if your infusion pump is not working properly.

Overdose symptoms may include extreme drowsiness, vision problems, confusion, speech problems, stiffness in your neck or back, nausea and vomiting, or loss of consciousness.

What should I avoid while using ziconotide?

Avoid drinking alcohol while you are using ziconotide. Ziconotide can cause side effects that may impair your thinking or reactions. Avoid driving or doing anything that requires you to be awake and alert.

Ziconotide 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. Call your doctor at once if you have a serious side effect such as:

• 
  

  problems with memory, speech, walking, or thinking;

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

  double vision or other vision problems;

  
  


• 
  

  new or worsening muscle pain, cramps, soreness, or weakness, and/or dark urine;

  
  


• 
  

  unusual bleeding or signs of infection around the microinfusion entry or catheter exit sites;

  
  


• 
  

  fever, headache, neck stiffness, chills, increased sensitivity to light, purple spots on the skin, nausea, vomiting, and/or seizure (convulsions);

  
  


• 
  

  extreme drowsiness or tired feeling, depressed mood;

  
  


• 
  

  feeling paranoid, hostile, disoriented, or confused;

  
  


• 
  

  strange sensations in your mouth;

  
  


• 
  

  hallucinations, unusual thoughts or behavior, thoughts of hurting yourself; or

  
  


• 
  

  feeling less alert, decreased consciousness (stupor or lack of response).

  
  

Less serious side effects may include:

• 
  

  headache, joint pain;

  
  


• 
  

  mild drowsiness or weakness;

  
  


• 
  

  dizziness, spinning sensation;

  
  


• 
  

  sleep problems, unusual dreams;

  
  


• 
  

  stomach pain, diarrhea, constipation, loss of appetite;

  
  


• 
  

  urinating less than usual; or

  
  


• 
  

  loss of balance or coordination.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Ziconotide Dosing Information

Usual Adult Dose for Pain:

Initial dose: No more than 2.4 mcg per day (0.1 mcg/hour) by intrathecal (IT) administration

The dosage should be titrated to patient response. Doses may be titrated upward by up to 2.4 mcg/day (0.1 mcg/hour) at intervals of no more than 2 to 3 times per week, up to a recommended maximum of 19.2 mcg/day (0.8 mcg/hour) by day 21. Dose increases in increments of less than 2.4 mcg/day (0.1 mcg/hour) and increases in dose less frequently than 2 to 3 times per week may be used. The average dose level at the end of a 21 day clinical study was 6.9 mcg per day (0.29 mcg/hour).

Usual Geriatric Dose for Pain:

The dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, and cardiac function, and of concomitant diseases or other drug therapy.

Initial dose: No more than 2.4 mcg per day (0.1 mcg/hour) by intrathecal (IT) administration

The dosage should be titrated to patient response. Doses may be titrated upward by up to 2.4 mcg/day (0.1 mcg/hour) at intervals of no more than 2 to 3 times per week, up to a recommended maximum of 19.2 mcg/day (0.8 mcg/hour) by day 21. Dose increases in increments of less than 2.4 mcg/day (0.1 mcg/hour) and increases in dose less frequently than 2 to 3 times per week may be used. The average dose level at the end of a 21 day clinical study was 6.9 mcg per day (0.29 mcg/hour).

What other drugs will affect ziconotide?

Before receiving ziconotide, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). Ziconotide can add to sleepiness caused by these other medications.

Also tell your doctor if you are taking a diuretic (water pill).

This list is not complete and there may be other drugs that can interact with ziconotide. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More ziconotide resources

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

• ziconotide Intrathecal Advanced Consumer (Micromedex) - Includes Dosage Information


• Ziconotide Professional Patient Advice (Wolters Kluwer)


• Ziconotide MedFacts Consumer Leaflet (Wolters Kluwer)


• Ziconotide Monograph (AHFS DI)


• Prialt Prescribing Information (FDA)


• Prialt Consumer Overview

Compare ziconotide with other medications

• Pain

Where can I get more information?

• Your pharmacist can provide more information ziconotide.

See also: ziconotide side effects (in more detail)

Jenloga

Pronunciation: KLOE-ni-deen
Generic Name: Clonidine
Brand Name: Examples include Catapresand Jenloga

Jenloga is used for:

Treating high blood pressure. It may be used alone or with other medicines. It may also be used for other conditions as determined by your doctor.

Jenloga is an alpha agonist. It works by relaxing blood vessels and decreasing heart rate, which lowers blood pressure.

Do NOT use Jenloga if:

• you are allergic to any ingredient in Jenloga

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

Before using Jenloga:

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

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


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


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


• if you have had a skin reaction to the patch form of Jenloga


• if you have kidney problems, heart problems, problems with the blood vessels in your heart or brain, or the blood disease porphyria, or if you will be having surgery


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

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

• Beta-blockers (eg, propranolol) because severe and sometimes life-threatening increased blood pressure may occur if Jenloga is suddenly stopped


• Calcium channel blockers (eg, verapamil) or digoxin because they may increase the risk of Jenloga's side effects


• Tricyclic antidepressants (eg, amitriptyline) because they may decrease Jenloga's effectiveness

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

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

• Take Jenloga by mouth with or without food.


• Take Jenloga on a regular schedule to get the most benefit from it.


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


• If you miss a dose of Jenloga, 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 Jenloga.

Important safety information:

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


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


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


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


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


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


• If you experience dry mouth, use sugarless candy or gum, or melt bits of ice in your mouth to help keep your mouth moist.


• Patients who wear contact lenses may notice dry eyes while using Jenloga. If you experience eye dryness or irritation, talk with your doctor about ways to lessen this effect.


• Do not suddenly stop taking Jenloga without talking to your doctor. Nervousness, agitation, confusion, tremor, and headache may occur. These may be followed by a rapid, severe rise in blood pressure. You may be at greater risk if you use high doses or if you also take a beta-blocker (eg, propranolol). If you need to stop taking Jenloga, follow your doctor's instructions for slowly decreasing your dose.


• Contact your doctor if you develop an illness that includes vomiting or if you vomit soon after you take Jenloga.


• Lab tests, including blood pressure, may be performed while you take Jenloga. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Jenloga with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness.


• Jenloga should be used with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Jenloga while you are pregnant. Jenloga is found in breast milk. If you are or will be breast-feeding while you use Jenloga, check with your doctor. Discuss any possible risks to your baby.

If you suddenly stop taking Jenloga, you may experience WITHDRAWAL symptoms, including nervousness, agitation, headache, tremor, flushing, fast heartbeat, chest tightness, and rapid increase in blood pressure. Do not suddenly stop taking Jenloga without checking with your doctor.

Possible side effects of Jenloga:

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

Constipation; dizziness; drowsiness; dry mouth; headache; nausea; tiredness; trouble sleeping.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); blurred vision or other vision changes; chest pain; decreased sexual desire or ability; fainting; fast, slow, or irregular heartbeat; mental or mood changes (eg, anxiety, agitation, depression, hallucinations); severe or persistent headache or dizziness; swelling of the hands, ankles, or feet.

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: Jenloga side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Accidental overdose of Jenloga is an increasing cause of poisoning in children 3 years of age and younger. Symptoms may include coma; decreased body temperature (feeling very cold); difficult or slow breathing; irritability; pinpoint pupils; seizures; severe or persistent dizziness or drowsiness; slow or irregular heartbeat; weakness.

Proper storage of Jenloga:

Store Jenloga at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Do not store in the bathroom. Store away from heat, moisture, and light. Keep Jenloga out of the reach of children and away from pets.

General information:

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


• Jenloga 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 Jenloga. 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 Jenloga resources

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

Compare Jenloga with other medications

• High Blood Pressure

Migranal nasal

Generic Name: dihydroergotamine (nasal) (dye HYE droe er GOT a meen)

Brand Names: Migranal

What is Migranal (dihydroergotamine (nasal))?

Dihydroergotamine is in a group of drugs called ergot alkaloids (ER-got AL-ka-loids). It works by narrowing the blood vessels around the brain.

Dihydroergotamine nasal is used to a treat migraine headache attack.

This medication will only treat a migraine headache that has already begun. It will not prevent headaches or reduce the number of attacks.

Dihydroergotamine nasal should not be used to treat common tension headaches or any headache that seems to be different from your usual migraine headaches.

Dihydroergotamine nasal may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Migranal (dihydroergotamine (nasal))?

This medication can harm an unborn baby or a nursing baby. Do not use dihydroergotamine nasal if you are pregnant or breast-feeding. Do not use this medication if you are allergic to dihydroergotamine or other ergot medicines, or if you have a history of heart disease, angina (chest pain), blood circulation problems, history of a heart attack or stroke, coronary artery disease, uncontrolled high blood pressure, severe liver or kidney disease, a serious infection, if you have recently had heart or blood vessel surgery. Using certain medications together with dihydroergotamine can cause severe decreases in blood flow and lead to dangerous side effects. Tell your doctor about all other medications you are using, especially antibiotics, antidepressants, heart or blood pressure medications, or medicines to treat HIV or AIDS.

Also tell your doctor about all of your medical conditions, especially breathing problems, high blood pressure, ischemic bowel disease, liver or kidney disease, or risk factors for coronary artery disease (such as diabetes, menopause, smoking, being overweight, having high blood pressure or high cholesterol, having a family history of coronary artery disease, being older than 40 and a man, or being a woman who has had a hysterectomy).

What should I discuss with my healthcare provider before using Migranal (dihydroergotamine (nasal))?

Do not use this medication if you are allergic to dihydroergotamine or other ergot medicine such as ergotamine (Ergomar, Ergostat, Cafergot, Ercaf, Wigraine), ergonovine (Ergotrate), methylergonovine (Methergine), or methysergide (Sansert).

Do not use dihydroergotamine nasal if you are pregnant or breast-feeding, or if you have:

• 
  

  a history of heart disease, angina (chest pain), blood circulation problems, coronary artery disease (hardening of the arteries), or history of a heart attack or stroke;

  
  


• 
  

  uncontrolled high blood pressure;

  
  


• severe liver or kidney disease;


• 
  

  a serious infection called sepsis; or

  
  


• 
  

  if you have recently had heart or blood vessel surgery (such as bypass surgery).

  
  

Using certain medications together with dihydroergotamine can cause even greater decreases in blood flow than dihydroergotamine used alone. A severe decrease in blood flow to the brain and other parts of the body can lead to dangerous side effects. Do not use dihydroergotamine if you are also using any of the following medications:

• 
  

  conivaptan (Vaprisol);

  
  


• 
  

  diclofenac (Arthrotec, Cataflam, Voltaren, Flector Patch, Solareze);

  
  


• 
  

  imatinib (Gleevec);

  
  


• 
  

  isoniazid (for treating tuberculosis);

  
  


• 
  

  an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), telithromycin (Ketek), or troleandomycin (Tao);

  
  


• 
  

  an antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend);

  
  


• 
  

  an antidepressant such as nefazodone;

  
  


• 
  

  heart or blood pressure medication such as diltiazem (Cardizem, Dilacor, Tiazac), nicardipine (Cardene), quinidine (Quinaglute, Quinidex, Quin-Release), or verapamil (Calan, Covera, Isoptin, Verelan); or

  
  


• 
  

  HIV/AIDS medicine such as amprenavir (Agenerase), atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase, Fortovase), or ritonavir (Norvir).

  
  

If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication. Before using dihydroergotamine, tell your doctor if you have:

• 
  

  breathing problems;

  
  


• 
  

  high blood pressure;

  
  


• 
  

  ischemic bowel disease;

  
  


• 
  

  liver disease;

  
  


• 
  

  kidney disease; or

  
  


• 
  

  coronary artery disease (or risk factors that include diabetes, menopause, smoking, being overweight, having high blood pressure or high cholesterol, having a family history of coronary artery disease, being older than 40 and a man, or being a woman who has had a hysterectomy).

  
  

FDA pregnancy category X. This medication can cause birth defects. Do not use dihydroergotamine if you are pregnant. Tell your doctor right away if you become pregnant during treatment. Use an effective form of birth control while you are using this medication. Dihydroergotamine passes into breast milk and may be harmful to a nursing infant. Dihydroergotamine may also decrease milk production. Do not use dihydroergotamine if you are breast-feeding a baby.

How should I use Migranal (dihydroergotamine (nasal))?

Use this medication exactly as prescribed by your doctor. Never use more than your prescribed dose of dihydroergotamine nasal. Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in treating your migraine attacks. Dihydroergotamine is not for daily use.

Dihydroergotamine nasal spray is absorbed quickly through your nasal passages and is for use only in the nose. The nasal spray liquid should not be injected into the body.

Your doctor may want to give your first dose of dihydroergotamine nasal in a hospital or clinic setting to quickly treat any serious side effects that occur.

Dihydroergotamine nasal comes in a bottle (vial) with a nasal sprayer attachment. Do not open the vial and attach the sprayer until you are ready to use the medication. A new vial and sprayer should be used for each new headache episode.

Before using the medication, prime the nasal spray by pumping exactly 4 sprays into the air.

Use the first dose of dihydroergotamine as soon as you notice headache symptoms, or after an attack has already begun. Use one spray in each nostril, and after 15 minutes use a second spray in each nostril, for a total of 4 sprays.

Do not tilt your head back while you are using the nasal spray, and do not sniff through your nose during use or just after use. Throw away the vial and sprayer after you finish using it to treat one headache episode, or no longer than 8 hours after opening the vial.

If you still have migraine symptoms after using a total of 4 sprays, call your doctor before using any more. Do not use more than 6 total sprays of dihydroergotamine nasal in any 24-hour period. Do not use more than 8 total sprays of this medication over a period of 7 days.

If you use dihydroergotamine nasal long-term, your doctor may want to check your heart function periodically using an electrocardiograph or ECG (sometimes called an EKG), a machine that measures electrical activity of the heart. This will help your doctor determine if it is still safe for you to use this medication. Do not miss any scheduled visits to your doctor.

Do not give this medication to anyone else, even if they have the same headache symptoms you have. Dihydroergotamine can be dangerous if it is used to treat headache in a person who has not been diagnosed by a doctor as having true migraine headaches. Store dihydroergotamine nasal at room temperature away from moisture and heat. Do not refrigerate or freeze the nasal spray. Do not use any stored dihydroergotamine if the expiration date on the label has passed.

What happens if I miss a dose?

Since dihydroergotamine is used on an as-needed basis, you are not likely to miss a dose.

Do not use more than 6 sprays of dihydroergotamine nasal per day or more than 8 sprays per week.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of dihydroergotamine can be fatal.

Overdose can cause stomach pain, nausea, vomiting, confusion, weak or shallow breathing, numbness and tingling or pain in your hands or feet, blue-colored fingers or toes, fainting, and seizure (convulsions).

What should I avoid while using Migranal (dihydroergotamine (nasal))?

Do not use dihydroergotamine nasal within 24 hours before or after using another migraine headache medicine, including:

• 
  

  another ergot medicine such as ergotamine (Ergomar, Ergostat, Cafergot, Ercaf, Wigraine), ergonovine (Ergotrate), methylergonovine (Methergine), or methysergide (Sansert); or

  
  


• 
  

  almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), sumatriptan (Imitrex), rizatriptan (Maxalt, Maxalt-MLT), or zolmitriptan (Zomig).

  
  

Grapefruit and grapefruit juice may interact with dihydroergotamine nasal and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Migranal (dihydroergotamine (nasal)) 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 dihydroergotamine and call your doctor at once if you have a serious side effect such as:

• 
  

  fast or slow heart rate;

  
  


• 
  

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

  
  


• 
  

  sudden numbness or weakness, sudden headache, confusion, or problems with vision, speech, or balance;

  
  


• 
  

  muscle pain in your arms or legs, leg weakness;

  
  


• 
  

  numbness or tingling and a pale or blue-colored appearance in your fingers or toes;

  
  


• 
  

  swelling or itching in any part of your body;

  
  


• 
  

  stomach cramps, diarrhea that may be bloody;

  
  


• 
  

  cough with stabbing chest pain and trouble breathing; or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

  
  

Less serious side effects may include:

• 
  

  pain, soreness, burning, tingling, or dryness in your nose or throat;

  
  


• 
  

  runny or stuffy nose, nosebleeds;

  
  


• 
  

  changes in your sense of taste;

  
  


• 
  

  headache, dizziness, drowsiness;

  
  


• 
  

  feeling anxious or depressed;

  
  


• 
  

  cold sweats; or

  
  


• 
  

  nausea, vomiting.

  
  

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 Migranal (dihydroergotamine (nasal))?

Many drugs can interact with dihydroergotamine. Below is just a partial list. Talk with your doctor before using dihydroergotamine nasal if you are also taking:

• 
  

  zileuton (Zyflo);

  
  


• 
  

  cold or allergy medications;

  
  


• 
  

  nicotine (Nicoderm, Nicorette);

  
  


• 
  

  diet pills, stimulants, or medication to treat ADHD (such as Ritalin or Adderall);

  
  


• 
  

  an antidepressant such as fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), nefazodone (Serzone), paroxetine (Paxil), sertraline (Zoloft), and others; or

  
  


• 
  

  heart or blood pressure medication such as atenolol (Tenormin), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others.

  
  

This list is not complete and there may be other drugs that can interact with dihydroergotamine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Migranal resources

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

Compare Migranal with other medications

• Cluster Headaches
• Migraine

Where can I get more information?

• Your pharmacist can provide more information about dihydroergotamine nasal.

See also: Migranal side effects (in more detail)

Atracurium besylate Injection BP 10 mg / ml

1. Name Of The Medicinal Product

Atracurium besylate Injection BP 10 mg/ml

2. Qualitative And Quantitative Composition

Atracurium besylate 10 mg/ml injection is a clear solution for intravenous injection in 2.5 ml, 5 ml, 10 ml and 25 ml ampoules containing 25 mg, 50 mg, 100 mg and 250 mg, respectively, of Atracurium besylate.

3. Pharmaceutical Form

Injection solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Atracurium is a highly selective, competitive (non-depolarising) neuromuscular blocking agent. It is indicated:

- As an adjunct to general anaesthesia, to relax the skeletal muscles during a wide range of surgical procedures and to facilitate controlled ventilation of the lungs.

- For administration by continuous infusion to maintain neuromuscular blockade during prolonged surgical procedures.

- To facilitate endotrachael intubation where subsequent maintenance of neuromuscular relaxation is required.

- To maintain muscular relaxation during Caesarean section.

4.2 Posology And Method Of Administration

Dosage of atracurium besylate should be individualised for each patient and administered by an experienced anaesthetist on the basis of body weight, sensitivity of the patient, other simultaneously used narcotics and duration of surgery. As with all neuromuscular blocking agents, monitoring of neuromuscular function is recommended during use of atracurium in order to determine the individual dosage requirements.

Atracurium besylate 10mg/ml injection should be administered by means of intravenous injection or infusion.

Use by intravenous injection in adults:

At the induction, the recommended dose range is 0.3 - 0.6mg/kg-body weight, depending on the desired duration of full block. This will provide adequate muscle relaxation for about 15 to 35 minutes.

Endotracheal intubation can usually be accomplished within 90 seconds of intravenous injection of 0.5 to 0.6mg/kg.

Supplementary doses of 0.1 to 0.2mg/kg may be used every 15 to 25 minutes as required to prolong full block. Successive supplementary doses do not lead to accumulation of neuromuscular blocking effect and may be administered at the end of a block (beginning of recovery).

Spontaneous recovery from the end of full block occurs in approximately 35 minutes when measured by the restoration of tetanic response to 95% of normal neuromuscular function.

The neuromuscular blockade produced by atracurium can be reversed, rapidly, by standard doses of anticholinesterase agents such as neostigmine or edrophonium, preceded or accompanied by atropine or glycopyrronium bromide, with no evidence or recurarisation.

Use by intravenous infusion in adults:

Following an initial bolus injection of 0.3 to 0.6mg/kg, atracurium may be administered by continuous intravenous infusion at a rate of 0.3 to 0.6mg/kg/h (5 to 10mcg/kg/min); the usual dose is approximately 6mcg/kg/min) to maintain neuromuscular block during long surgical procedures. When necessary the dosage can be adjusted using an appropriate method, for instance the tetany response.

When possible, infusions of atracurium should be administered through a separate infusion line.

During cardiopulmonary bypass surgery, atracurium may be administered by infusion at the recommended infusion rates. If hypothermia is induced to a body temperature of 25^o to 26^oC, the rate of inactivation of atracurium is reduced and full neuromuscular block may be maintained by using approximately half the infusion rate during normothermia. The usual dose is approximately 3.4mcg/kg/min.

When atracurium is diluted with the following solutions, giving concentrations of 0.5 to 0.9mg/ml, the drug will be stable in daylight at temperatures of up to 30°C for the following time periods:

Infusion solution	Stable during
Sodium Chloride Intravenous Infusion (0.9% m/V)	24 h
Glucose Intravenous Infusion (5%m/V)	8 h
Ringer's injection	8 h
Sodium Chloride (0.18%m/V) and Glucose (4% m/V) Intravenous Infusion	8 h
Compound sodium Lactate Intravenous Infusion	4 h

Use in children:

For children over the age of 1 month, the dosage is similar to that in adults on a mg per kg body weight basis.

Use in the elderly:

Atracurium besylate may be used at standard dosage, although the size of the initial dose should be at the lower end of the dose range and the drug should be administered slowly.

Use in patients with diminished renal and/or hepatic function:

Atracurium besylate may be used at standard dosage for all degrees of renal or hepatic impairment, including end stage failure of these organs.

Use in patients with cardiovascular diseases:

In patients with clinically significant cardiovascular disease, the initial dose of atracurium besylate should be administered over a period of 1 to 2 minutes.

Use in burn patients:

Patients who suffer burn injury may develop resistance to non-depolarising neuromuscular blocking drugs, including atracurium, and increased doses may be required, depending on the extent of the burn and the time elapsed since its occurrence.

Long-term Use in Intensive Care Unit:

When there is a need for long-term controlled ventilation with use of atracurium in the Intensive Care Unit, the benefit-risk ratio of neuromuscular blockade must be considered.

Experience with muscular relaxants like atracurium in the Intensive Care Unit shows that there is a wide interpatient variability in dosage requirements and theses requirements may decrease or increase with time.

On the basis of experience with atracurium in the Intensive Care Unit, it is likely that a dose increase may be required with long-term use.

It is not known whether haemodialysis, haemoperfusion or haemofilteration influence the plasma levels of atracurium or its metabolites.

4.3 Contraindications

Atracurium is contraindicated in patients known to have or with suspected hypersensitivity to the active and/or the excipients.

4.4 Special Warnings And Precautions For Use

In common with all neuromuscular blocking agents, atracurium paralyses the respiratory as well other skeletal muscles (e.g. muscles of arms, legs, eyelids, and mouth) without having an effect on consciousness. Consequently, the drug should be administered only with adequate anaesthesia and only by an experienced anaesthetist familiar with its pharmacological properties. All facilities for endotracheal intubation and artificial respiration should be available for immediate use.

The neuromuscular block of atracurium is increased during hypothermia and decreases when rewarming the patient.

Atracurium should be adminstered with care to patients with myasthenia gravis, other neuromuscular diseases, and severe electrolyte imbalance, in view of the increased sensitivity of these patients to the effects of non-depolarising neuromuscular agents. Severe acidosis may result in a slight prolongation of action of atracurium.

In common with other neuromuscular blocking drugs, there is the potential for histamine release in susceptible patients during administration of atracurium. Therefore, caution should be exercised when administering atracurium to patients with a history suggesting an increased sensitivity to the effects of histamine.

It should be considered that, especially in patients with a history of allergy or asthma, bronchospasm may occur sporadically after the administration of atracurium. In such cases, the use of atracurium should be monitored very carefully.

Atracurium besylate should be administered slowly or in divided doses over a period of 1 to 2 minutes in patients who may be especially sensitive to a decrease in arterial blood pressure, e.g. patients with hypovolaemia, and in patients who are more susceptible to the effects of transient hypotonic conditions, such as patients with severe cardiovascular disease.

Patients with carcinomatosis especially when associated with bronchial carcinoma may exhibit a marked sensitivity to neuromuscular blocking agents, and the neuromuscular block produced may respond poorly to anticholinesterase agents.

Special care must be taken to ensure that there is adequate respiratory exchange before the patient is discharged from the care of the anaesthetist.

Atracurium does not show any significant vagal or ganglionic blocking effects in the recommended dose range. Consequently, when used in the recommended dose range, atracurium has no clinically significant effects on the heart rate.

Vagal stimulation during surgical procedures or bradycardia produced by other anaesthetic agents will not be counteracted by atracurium and, therefore, bradycardias may be more common with atracurium than with other muscle relaxants.

Atracurium is not recommended in children under the age of one month since not enough experience has been acquired in this age group so far.

Atracurium besylate (10mg/ml injection) is hypotonic and therefore should not be administered through an infusion line of a blood transfusion. Due to the hypotonic condition of the solution, it is recommended to dilute the intravenous injection 1:1 with the in 6.3 mentioned infusion solutions, as a precaution when used in children.

Atracurium besylate should not be mixed with thiopentone or any alkaline solutions in the same syringe since the high pH would cause inactivation of atracurium.

When a small vein is selected as the injection site, atracurium besylate (10mg/ml injection) should be flushed through the vein with physiological saline after injection. Where other (anaesthetic) drugs are administered through the same in–dwelling needle or cannula as atracurium, it is important that each drug is flushed through with physiological saline or water for injections in adequate volume.

Animal studies in malignant hyperthermia in susceptible species (Swine) and clinical studies in susceptible patients indicate that atracurium does not trigger malignant hyperthermia.

Atracurium can be administered during ophthalmic surgery since the drug does not influence the intra-ocular pressure.

Patients with a purulent intrathoracic disease may show a reduction in neuromuscular potency of atracurium.

Patients undergoing surgical procedures of a short duration may be at risk of inappropriately having an early tracheal extubation, as there is a risk of postoperative residual neuromuscular blockade.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The neuromuscular blocking action of atracurium may be enhanced by concomitant use of inhalational anaesthetic agents; such as halothane, isoflurane and enflurane. Furthermore, there are a number of drugs, which may enhance and/or prolong the neuromuscular blockade when used simultaneously with atracurium:

- Certain antibiotics including the aminoglycosides (such as neomycin), polypeptide antibiotics (such as polymyxin), spectinomycin, tetracycline, lincomycin and clindamycin

- anti-arrhythmic agents: procainamide, quinidine, lidocaine (lignocaine)

- beta-adrenoceptor blocking agents: propranolol

- Calcium-channel blocking agents

- Diuretics: furosemide (frusemide) and possibly mannitol, thiazide diuretics, acetazolamide

- Magnesium sulphate

- Ketamine

- Lithium salts

- Ganglionic blocking agents, trimetaphan, and hexamethonium

In rare cases, certain agents may aggravate the symptoms of an existing myasthenia gravis, unmask latent myasthenia gravis, or cause this disease itself. In such cases, an increased sensitivity to atracurium should be expected. These agents include:

- various antibiotics

- Anti-arrhythmic agents: procainamide, quinidine

- Beta-adrenoceptor blocking agents: propranolol, oxprenolol

- Anti-rheumatic agents: chloroquine, D-penicillamine

- Trimetaphan

- Steroids

- Chlorpromazine

- Lithium

- Phenytoin

In patients who are receiving long-term treatment with anti-epileptic agents, the onset of non-depolarising neuromuscular block is likely to be lengthened and the duration of the block shortened.

Administration of combinations of other non-depolarising neuromuscular blocking drugs with atracurium may produce a degree of neuromuscular blockade, which is larger than expected after administration of an equipotent total dose of atracurium alone. This synergistic effect can differ from one combination of agents to another.

Depolarising muscle relaxants, such as suxamethonium, should not be administered to prolong the neuromuscular blocking effect of non-depolarising agents, such as atracurium, since the combined action of these drugs may result in a prolonged and complex neuromuscular blockade (“mixed block” or “phase II-block”) which is difficult to reverse with anticholinesterase agents.

4.6 Pregnancy And Lactation

Insufficient information is available about the use of atracurium in pregnant women to be able to evaluate the possible harmfulness. So far, in animal tests no indications have been found showing harmful effects on the foetal development. Therefore, in common with all neuromuscular blocking drugs, atracurium should be used during pregnancy only if the potential benefit to the mother outweighs any potential risk to the foetus.

Atracurium besylate may be administered to maintain muscle relaxation during Caesarean section. Following recommended doses, atracurium does not cross the placental barrier in clinically significant amounts. It is not known to what extent metabolites of atracurium cross the placental barrier.

It is not known whether atracurium is excreted in human milk. No atracurium was found in human milk after its use during Caesarean section. However, from a safety point of view temporary discontinuation of breast-feeding is recommended for at least 24 hours following administration of atracurium.

4.7 Effects On Ability To Drive And Use Machines

Not relevant, in view of the therapeutic indication for this product.

4.8 Undesirable Effects

In common with most neuromuscular blocking agents, atracurium may have the potential for histamine release in sensitive patients. Associated with the use of atracurium, there have been reports of skin flushing, transient hypotension and, rarely, bronchospasm, which have been attributed to histamine release. Moreover, tachycardia was observed. In seldom cases skin rash occurs. Anaphylactic reactions and laryngospasm appear very rarely.

4.9 Overdose

Symptoms

Prolonged muscle relaxation and its effects are the main symptoms of an overdosage of atracurium.

Treatment

In case of overdosage, controlled ventilation must be maintained until adequate spontaneous respiration has returned. Since atracurium does not influence consciousness, the patient can be fully sedated. When there is evidence of spontaneous recovery, an anticholinesterase agent such as neostigmine or edrophonium in conjunction with atropine or glycopyrronium bromide, may be administered to hasten recovery.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Atracurium is a selective competitive (non-depolarising) neuromuscular blocking agent. It prevents neurotransmission by competition with acetylcholine for cholinergic receptor sites of the motor end plate, but does not produce any stimulation of the muscle by itself. This results in muscle relaxation.

5.2 Pharmacokinetic Properties

The onset and duration of action of atracurium besylate are dose dependent.

The effect of the recommended dose of atracurium besylate occurs within 2 minutes after administration and maximum neuromuscular blockade is usually reached within 3 to 5 minutes. Good intubation conditions are reached within 1.5 to 2 minutes in most patients. The recommended dose of 0.3 to 0.6mg/kg for adults causes a relaxation of 15 to 35 minutes. Supplementary doses of 0.1 to 0.2mg/kg can prolong the duration of the effect for 15 to 45 minutes. After a dose of 0.3mg atracurium besylate per kg in humans, a plasma concentration of approximately 3mcg/ml was measured after 3 minutes.

Atracurium undergoes degradation via Hofmann elimination, a non-enzymatic breakdown process occurring at physiological pH and temperature, and also by ester hydrolysis by non-specific plasma esterases.

The duration of action of atracurium is not altered to any significant extent by variations in patient's blood pH and body temperature within the physiological range. The metabolites formed have a low activity and are produced in such small amounts that the contribution of the metabolites to the effect of atracurium can be neglected.

Atracurium produces a weak inhibition of acetylcholinesterase and butyrylcholinesterase in vitro with no clinical significance. Investigation of plasma from patients with pseudocholinesterase deficiency has shown that the inactivation of atracurium is continued unaffected.

The duration of the neuromuscular blocking effect of atracurium does not depend on metabolism and elimination by liver or kidneys. Consequently, the duration of action of atracurium besylate is not likely to be influenced by impaired renal, hepatic or circulatory function.

Plasma protein binding of atracurium besylate is 82%. Plasma proteins do not influence the rate nor the mode of atracurium besylate degradation.

The elimination half-life of atracurium besylate is between 20 and 30 minutes.

5.3 Preclinical Safety Data

Carcinogenicity: Carcinogenicity studies have not been performed.

Teratogenicity: Animal studies indicate that atracurium has no significant effects on foetal development

Fertility: Fertility studies have not been performed.

Mutagenicity: Atracurium has been evaluated in short-term mutagenicity tests. It was not mutagenic in either the in vitro Ames salmonella assay at concentrations up to 1,000mcg/plate or in an in vivo rat bone marrow assay at doses up to those that produced neuromuscular blockade. In a second in vitro test, the mouse lymphoma assay, mutagenicity was not observed at doses up to 60mcg/ml, which killed up to 50% of the treated cells. It was moderately mutagenic at concentrations of 80mcg/ml without metabolic activation and was weakly mutagenic at very high concentrations (1,200mcg/ml) when metabolising enzymes were added at both concentrations, over 80% of the cells were killed.

In view of the nature of human exposure to atracurium, the mutagenic risk in surgical patients undergoing muscle relaxation with atracurium must be considered negligible.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Atracurium besylate 10mg/ml injection contains benzenesulfonic acid (to adjust the pH to 3.2-3.7) and water for injections. The injection does not contain any preservatives and is filled in ampoules under nitrogen atmosphere. The solution is strongly hypotonic.

6.2 Incompatibilities

Atracurium injection should not be mixed in the same syringe with thiopentone or alkaline solutions since the high pH may inactivate the drug.

6.3 Shelf Life

The shelf life of Atracurium besylate 10 mg/ml injection is 1.5 year.

The expiry date (month and year) is printed on the package after the words "do not use after" and on the ampoules after "Exp".

When atracurium is diluted with the following solutions, giving concentrations of 0.5 to 0.9 mg/ml, the drug will be stable in daylight at temperatures of up to 30°C for the following time periods:

Infusion Solution	stable during
Sodium Chloride Intravenous Infusion (0.9% m/V)	24 h
Glucose Intravenous Infusion (5% m/V)	8 h
Ringer's Injection	8 h
Sodium Chloride (0.18% m/V) and Glucose (4% m/V) Intravenous Infusion	8 h
Compound Sodium Lactate Intravenous Infusion	4 h

Any unused solution in opened ampoules should be discarded immediately after use.

6.4 Special Precautions For Storage

The ampoules should be stored in the original packaging, protected from light, at 2 - 8°C (do not freeze). When Atracurium besylate 10 mg/ml injection is stored for one month at 25°C the loss of potency will be 5%.

Keep all medicines out of the reach of children

6.5 Nature And Contents Of Container

Ampoules of 2.5, 5 and 10ml (both packaged per 5 or 10 pieces) containing 25, 50 and 100mg of Atracurium besylate, respectively. Ampoules of 25 ml (packaged per 2, 5 or 10 pieces) containing 250 mg of Atracurium besylate.

6.6 Special Precautions For Disposal And Other Handling

Finger protection should be used when ampoules are opened.

Administrative Data

7. Marketing Authorisation Holder

Antigen International Limited

Roscrea

Co Tipperary

Ireland

8. Marketing Authorisation Number(S)

PL 02848/0205

9. Date Of First Authorisation/Renewal Of The Authorisation

04/07/2006

10. Date Of Revision Of The Text

04/07/2006

Strepsils (Reckitt Benckiser Healthcare (UK) Ltd)

1. Name Of The Medicinal Product

Strepsils

2. Qualitative And Quantitative Composition

Amylmetacresol BP	0.6mg
2,4-Dichlorobenzyl alcohol HSE	1.2mg

3. Pharmaceutical Form

A red circular lozenge.

4. Clinical Particulars

4.1 Therapeutic Indications

For the symptomatic relief of mouth and throat infections.

4.2 Posology And Method Of Administration

For oral administration.

Adults and children (over 6 years old):

One lozenge to be dissolved slowly in the mouth every 2-3 hours up to a maximum of 12 lozenges in 24 hours.

Not suitable for children under 6 years.

Elderly: There is no need for dosage reduction in the elderly.

4.3 Contraindications

Hypersensitivity to any of the ingredients.

4.4 Special Warnings And Precautions For Use

Keep all medicines out of the reach of children.

If symptoms persist consult your doctor.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically significant interactions are known.

4.6 Pregnancy And Lactation

The safety of Strepsils Original Flavour has not been established, but is not expected to constitute a hazard.

4.7 Effects On Ability To Drive And Use Machines

No adverse effects are known.

4.8 Undesirable Effects

Occasional hypersensitivity reactions.

4.9 Overdose

Overdosage should not present a problem other than gastrointestinal discomfort. Treatment should be symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

2,4-Dichlorobenzyl alcohol and amylmetacresol have antiseptic properties.

5.2 Pharmacokinetic Properties

None available.

5.3 Preclinical Safety Data

None available.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Star Anise oil

Peppermint oil

Menthol natural or menthol synthetic

Tartaric acid gran 571 GDE

Ponceau 4R edicol E124

Carmoisine edicol E122

Liquid Sucrose

Liquid Glucose

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

36 months for lozenges packed in blister strips within a carton.

24 months for blister packs attached to a stencilled card.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

A blister push-through pack consisting of 15 or 20µm hard temper aluminium foil heat-sealed to a 250µm PVC/40gms PVDC blister. The tray contains an appropriate number of lozenges to give pack sizes of 6, 8, 10, 12, 16, 18, 20, 22, 24, 32, 36 and 720 lozenges in a cardboard carton or a flow wrap composed of PET/aluminium foil/polyethylene

A blister push-through pack consisting of 15 or 20µm hard-temper aluminium foil heat-sealed to a 250µm PVC/40gms PVDC blister. Two, four or six blisters are attached to a stencilled card.

Jar of polypropylene/ethyl-vinyl hydroxide (EVOH) barrier/ polypropylene laminate with a polypropylene cap fitted with an aluminium faced pulpboard liner, or a HDP jar with a tinplate cap fitted with an aluminium faced pulpboard liner. Pack size 1800 lozenges.

A blister push-through pack consisting of 15 or 20µm hard temper aluminium foil heat-sealed to a 250µm PVC/40gms PVDC blister. The tray contains an appropriate number of lozenges to give a pack size of 8 lozenges in a wrap around cardboard carton with tamper-evident seal.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Reckitt Benckiser Healthcare (UK) Ltd

Slough

SL1 3UH

8. Marketing Authorisation Number(S)

PL 00063/0396

9. Date Of First Authorisation/Renewal Of The Authorisation

19^th March 2010

10. Date Of Revision Of The Text

March 2010

Antimalarial agents

Antimalarials agents are drugs effective in the treatment of malaria. Malaria is an infectious disease caused by the bite of an anopheles mosquito infected with certain protozoans. The best way to prevent malaria is by taking antimalarial drugs prophylactically prior to entering an endemic area.

Antimalarial agents are classified according to their action against different stages of the life cycle of the parasite. Certain antimalarial agents are more effective in the acute attack of malaria, and generally more that one agent will be used simultaneously to avoid resistance. Some antimalarial agents are used as prophylactic agents; they kill the parasite when it enters the host.

See also

• antimalarial combinations
• antimalarial quinolines
• miscellaneous antimalarials

Drug List:

Doxorubicin Hydrochloride for Injection 10 mg and 50 mg

1. Name Of The Medicinal Product

Doxorubicin Hydrochloride for Injection 10 mg and 50 mg

2. Qualitative And Quantitative Composition

Active Constituent		10 mg	50 mg
Doxorubicin	USP	10.0 mg	50.0 mg

3. Pharmaceutical Form

Sterile freeze dried powder for injection.

4. Clinical Particulars

4.1 Therapeutic Indications

Doxorubicin has been used successfully in the treatment of neoplastic conditions such as acute leukaemia, soft tissue and osteogenic sarcomas, breast carcinoma, lymphomas, bronchogenic (lung) carcinoma. It has also been used in the treatment of paediatric malignancy. Doxorubicin is frequently used in combination chemotherapy regimen involving other cytotoxic drugs. Doxorubicin can be used in the treatment of non-metastatic transitional cell carcinoma, carcinoma in situ and papillary tumours of the bladder, by intravesical administration.

4.2 Posology And Method Of Administration

When used as a single agent, the recommended dosage is 60-75 mg/m² body surface area, as a single intravenous injection administered at 21 day intervals. If using body weight to calculate the dose, then dosages of 1.2 – 2.4 mg/kg are recommended.

It has been shown that giving doxorubicin as a single dose every three weeks greatly reduces the distressing toxic effect, mucositis. However, there are some regimens which divide the dose over three successive days (20-25 mg/m² or 0.4-0.8 mg/kg). It is thought that this regimen has greater effectiveness although at a cost of higher toxicity.

Administration of doxorubicin in a weekly regimen has been shown to be as effective as the three weekly regimen. The recommended dosage is 20 mg/m² once a week although objective responses have been seen at 6-12 mg/m². This regimen of weekly dosing also reduces the incidence of cardiotoxicity.

It is particularly important to reduce the dose of doxorubicin if it is used in combination with other drugs with a similar toxicity profile. The recommended lifetime cumulative dose limit is 450-550 mg doxorubicin hydrochloride/m² body surface area.

It is recommended that doxorubicin be slowly administered into the tubing of a freely running intravenous infusion of Sodium Chloride Injection 0.9% or 5% Dextrose Injection. The tubing should be attached to a Butterfly needle inserted preferably into a large vein. The rate of administration is dependent on the size of the vein and the dosage. However the dose should be administered in not less than 3 to 5 minutes. This technique minimises the risk of thrombosis or perivenous extravasation which can lead to severe cellulitis and vesication.

Intravenous infusion is not advised due to the tissue damage that may occur if the infusion infiltrates the tissues. If a central vein catheter is used then infusion of doxorubicin in Sodium Chloride 0.9% Injection is advised.

Local erythematous streaking along the vein as well as facial flushing may be indicative of too rapid administration. A burning or stinging sensation may be indicative of perivenous infiltration and the infusion should be immediately terminated and restarted in another vein. Doxorubicin should not be mixed with heparin since it has been reported that these drugs are incompatible to the extent that a precipitate may form. Until specific compatibility data are available, it is not recommended that doxorubicin be mixed with other drugs.

Intravesical administration

This technique may be used for the treatment of transitional cell carcinoma, papillary bladder tumours and carcinoma in situ. It should not be used for invasive tumours of the bladder which have penetrated the bladder wall.

Many regimens are in use, making interpretation difficult, but the following procedure may be a helpful guide:

1. Patient should be instructed not to drink fluids for 12 hours prior to the examination.

2. Dissolve 50 mg of doxorubicin in 50 ml of normal saline and instil via the catheter into the bladder.

3. The catheter should be removed and the patient instructed to be on one side. At 15 minute intervals the patient should make a quarter turn over a 1 hour period. At the end of this period, the patient may void.

4. The procedure may be repeated at monthly intervals.

Intraarterial administration

Doxorubicin hydrochloride has been administered as an intra-arterial infusion in an attempt to produce local intense activity and reduce systemic toxicity. However it must be recognised that this route of administration is potentially extremely hazardous and can lead to widespread necrosis of perfused tissue unless careful precautions are taken. Intraarterial administration should be undertaken only by experienced professionals.

Paediatric

Adult dosage regimens may be suitable for paediatric cases, but may need to be reduced.

Geriatric

It is recommended that the total cumulative dose of doxorubicin for adults aged 70 or older be restricted to 450 mg/m² body surface area. Adult doses may be suitable for geriatric patients, but may need to be reduced.

Impaired Hepatic Function

Doxorubicin is metabolised by the liver and excreted in bile. Impairment of liver function results in slower excretion of the drug and consequently increased retention and accumulation in the plasma and tissues, resulting in enhanced clinical toxicity.

Doxorubicin dosage must be reduced if hepatic function is impaired according to the following table:

Serum Bilirubin Levels	BSP Retention	Recommended Dose
1.2 – 3.0 mg/100 ml	9 – 15%	50% normal dose
Over 3.0 mg/100 ml	Over 15%	25% normal dose

Impaired Renal Function

Doxorubicin and metabolites are excreted in the urine to a minor degree and there are no clear indications that the pharmacokinetics or toxicity of doxorubicin are altered in patients with impaired renal function.

4.3 Contraindications

Dosage should not be repeated in cases of bone marrow depression or buccal ulceration or buccal burning sensation, which can precede ulceration.

Experienced Physician: Doxorubicin should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.

4.4 Special Warnings And Precautions For Use

WARNINGS

Cardiac Toxicity: Special attention must be given to the cardiac toxicity exhibited by doxorubicin. This may present as tachycardia or ECG changes including supraventricular tachycardia. Severe cardiac failure may occur suddenly, without premonitory ECG changes.

It is recommended that the cumulative total lifetime dose of doxorubicin (including related drugs such as daunorubicin) should not exceed 450 – 550 mg/sq m body surface area. Above this dosage, the risk of irreversible congestive cardiac failure increases greatly. Total dose should also take account of any previous or concomitant mediastinal irradiation, other anthracycline chemotherapy or concurrent high dose cyclophosphamide, which may also exhibit cardiotoxic effects.

Congestive heart failure and/or cardiomyopathy may be encountered several weeks after discontinuation of doxorubicin therapy and for this reason extreme care should be taken in patients with existing associated heart disease.

Cardiac failure is often not favourably affected by presently known medical or physical therapy for cardiac support. Early clinical diagnosis of drug induced heart failure appears to be essential for successful treatment with digitalis, diuretics, low salt diet and bed rest. Severe cardiac toxicity may occur precipitously without antecedent ECG changes. Base line ECG and periodic follow up ECG during and immediately after active drug therapy is an advisable precaution. Transient ECG changes, such as T-wave flattening, S-T depression and arrhythmias are not considered indications for suspension of doxorubicin therapy. A persistent reduction in the voltage of the QRS wave is presently considered more specifically predictive for cardiac toxicity. If this occurs, the benefit of continued therapy must be carefully evaluated against the risk of producing irreversible cardiac damage.

Bone Marrow Depression: There is a high incidence of bone marrow depression, primarily of leucocytes, requiring careful haematological monitoring. With the recommended dosage schedule, leucopenia is usually transient, reaching its nadir at 10 – 14 days after treatment, with recovery usually occurring by the 21^st day. White blood cell counts as low as 1000/cubic mm are to be expected during treatment with appropriate doses of doxorubicin. Red blood cell and platelet levels should also be monitored, since they may also be depressed.

Haematologic toxicity may require dose reduction or suspension or delay of doxorubicin therapy.

Immunosuppression: Doxorubicin is a powerful but temporary immunosuppressant agent. Appropriate measures should be taken to prevent secondary infection.

Severe Myelosuppression: Persistent severe myelosuppression may result in superinfection or haemorrhage.

Enhanced Toxicity: It has been reported that doxorubicin may enhance the severity of the toxicity of anticancer therapies, such as cyclophosphamide induced haemorrhagic cystitis, mucositis induced by radiotherapy and hepatotoxicity of 6-mercaptopurine.

Infertility: Doxorubicin may cause infertility during the time of drug administration. Although ovulation and menstruation appear to return after termination of therapy, there is no information about the restoration of male fertility.

Hepatic Impairment: Toxicity to recommended doses of doxorubicin is enhanced by hepatic impairment. It is recommended that an evaluation of hepatic function be carried out prior to individual dosing, using conventional clinical laboratory tests such as AST, ALT, alkaline phosphatase, bilirubin and BSP. If required, dosage schedules should be reduced accordingly. (See DOSAGE and ADMINISTRATION).

Extravasation: On intravenous administration of doxorubicin, a stinging or burning sensation signifies extravasation and, even if blood return from aspiration of the infusion needle is good, the injection or infusion should be immediately terminated and restarted in another vein.

Should extravasation occur, stop the infusion immediately and apply ice packs to the injection site. Local injection of dexamethasone or hydrocortisone may be used to minimise local tissue necrosis. Hydrocortisone cream 1% may also be applied locally.

PRECAUTIONS

Initial treatment with doxorubicin requires close observation of the patient and extensive laboratory monitoring.

It is strongly recommended therefore, that patients be hospitalised at least during the first phase of treatment. Blood count and liver function tests should be carried out prior to each doxorubicin treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Not applicable

4.6 Pregnancy And Lactation

Use In Pregnancy

The drug is embryotoxic and teratogenic in rats and embryotoxic and abortifacient in rabbits, and trace amounts of the drug have been found in mouse foetuses and in one aborted human foetus. Although there is no conclusive evidence, there is data which suggests that doxorubicin may harm the foetus. It is therefore recommended that doxorubicin is not administered to women who are pregnant.

Use In Lactation

Doxorubicin is distributed into milk. Experimental data suggests that doxorubicin may harm the infant and should therefore not be administered to mothers who are breast feeding.

4.7 Effects On Ability To Drive And Use Machines

Not known.

4.8 Undesirable Effects

ADVERSE REACTIONS

More Common Reactions

Cardiovascular: Cardiotoxicity i.e. cardiomyopathy, congestive heart failure, supraventricular tachycardia.

Dermatological: Doxorubicin extravasation, skin necrosis, cellulitis, vesication, phlebitis, reversible alopecia, erythematous streaking along the vein proximal to the site of injection, phlebosclerosis. Hair growth returns to normal after cessation of treatment.

Gastrointestinal: Nausea and vomiting, mucositis (stomatitis and oesophagitis), diarrhoea. Mucositis is a frequent and painful complication of doxorubicin treatment. Mucositis most commonly develops 5 to 10 days after treatment, and typically begins as a burning sensation in the mouth and pharynx. It may involve the vagina, rectum and oesophagus, and progress to ulceration with risk of secondary infection and usually subsides in 10 days. Retrospective comparison of the incidence of mucositis suggests that it is less frequent as the intervals between doses increase. Mucositis may be severe in patients who have had previous irradiation to the mucosae.

General: Dehydration, facial flushing (if an injection has been given too rapidly). Administration of doxorubicin may cause red colouration of the urine. Patients should be advised that this is no cause for alarm.

Haematological: Myelosuppression, leucopenia.

Less Common Reactions

Dermatological: Urticarial rash, hyperpigmentation of nailbeds and dermal increases (primarily in children in a few cases), recall of skin reaction due to prior radiotherapy.

General: Chills and fever, anorexia, anaphylaxis

Haematological: Leucopenia, thrombocytopenia, anaemia. Myelosuppression is more common in patients who have had extensive radiotherapy, bone infiltration by tumour, impaired liver function (when appropriate dosage reduction has not been adopted. See DOSAGE: WITH IMPAIRED HEPATIC FUNCTION) and simultaneous treatment with other myelosuppressive agents. The nadir (time from treatment to peripheral blood evidence of maximal myelosuppression) of leucopenia and thrombocytopenia is 10 to 15 days after treatment, and counts return to normal before day 21.

Nervous System: Drowsiness

Ocular: Conjunctivitis.

Renal: Renal damage.

4.9 Overdose

Clinical Features: The symptoms of overdosage are likely to be an extension of doxorubicin's pharmacological action. Single doses of 250 mg and 500 mg of doxorubicin have proved fatal. Such doses may cause acute myocardial degeneration within 24 hours, and severe myelosuppression, the greatest effects of which are seen between 10 and 15 days after administration.

Delayed cardiac failure may occur up to six months after the overdose. Patients should be monitored carefully and if symptoms appear, conventional treatment started.

Management: Symptomatic supportive measures should be instituted. Particular attention should be given to prevention and treatment of possible severe haemorrhage or infections secondary to severe, persistent bone marrow depression. Blood transfusion and reverse barrier nursing may be considered.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Doxorubicin hydrochloride is a cytotoxic anthracycline antibiotic.

Although not completely elucidated, the mechanism of action of doxorubicin is related to its ability to bind to DNA and inhibit nucleic acid synthesis. Cell culture studies have demonstrated rapid cell penetration and perinucleolar chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, mutagenesis and chromosomal aberrations.

The specificity of doxorubicin toxicity appears to be related primarily to proliferative activity of normal tissue. Thus, bone marrow, gastro-intestinal tract and gonads are the main normal tissues damaged.

Doxorubicin is not suitable for oral administration as less than 5% of the drug is absorbed.

5.2 Pharmacokinetic Properties

Pharmacokinetic studies show the intravenous administration of normal or radiolabelled doxorubicin for injection is followed by rapid plasma clearance and significant tissue binding. No information on plasma-protein binding of doxorubicin is available.

The metabolism and disposition of doxorubicin is still to be defined. The drug is metabolised predominantly by the liver to doxorubicinol and several aglycone metabolites. It should be noted that several of the metabolites are cytotoxic. However, it is not certain whether any are more cytotoxic than the parent compound. High levels of metabolites appear rapidly in plasma and undergo a distribution phase with a measurable short initial half-life. Metabolism may be impaired in patients with abnormal liver function.

The disappearance of doxorubicin and its metabolites from the plasma follows a triphasic pharmacokinetic pattern with a mean half-life of the first phase of 12 minutes, of a second phase of 3.3 hours and a prolonged third phase of 29.6 hours.

Urinary excretion of doxorubicin hydrochloride and its metabolites is prolonged and accounts for only 5% of the drug excreted during the first 5 days. Approximately 50% of an administered dose is excreted in bile.

Impairment of liver function results in slower excretion, and consequently, increased retention and accumulation in plasma and tissues. Doxorubicin does not cross the blood brain barrier. However it is known to cross the placenta barrier.

5.3 Preclinical Safety Data

There is no pre-clinical data of relevance to the prescriber which are additional to that already included in other section of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Other Constituent	10 mg	50 mg
Lactose monohydrate BP	52.6 mg	263.1 mg

There is no overage included in the above formulations.

6.2 Incompatibilities

Doxorubicin should not be mixed with heparin since it has been reported that these drugs are incompatible to the extent that a precipitate may form. Until specific compatibility data are available, it is not recommended that doxorubicin be mixed with other drugs.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 25°C and protect from light.

6.5 Nature And Contents Of Container

10 ml or 30 ml clear, Type I conventional glass vials and Onco-Tain^® vials, with 13 mm or 20 mm, 1018 Style, West Type 1816 grey rubber closures, aluminium seal and plastic 'flip-off' tops.

6.6 Special Precautions For Disposal And Other Handling

Doxorubicin is a potent cytotoxic agent which should only be prescribed, prepared and administered by professionals who have been trained in the safe use of the preparation. The following guidelines should be followed when handling, preparing and disposing of doxorubicin.

Preparation

1. Reconstitution of powder, transfer to syringes or infusion bags should be carried out in designated areas, preferably a laminar flow station.

2. Personnel must be adequately protected with suitable clothing, gloves, mask and eye shield.

3. Pregnant women should be excluded from handling cytotoxic agents.

Contamination

1. In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat transient stinging of skin. Medical advice should be sought if the eyes are affected.

2. In the event of spillage treat with 1% Sodium Hypochlorite solution using a cloth/sponge kept in the designate area. Rinse twice with water. Put all cloths into a plastic bag and seal for incineration.

Disposal

All items used during preparation or administration including syringes, containers, absorbent materials, residual solutions should all be placed in a thick plastic bag and incinerated at 700°C.

Preparation of the Injection

The contents of the vial should be reconstituted with Water for Injection BP, Sodium Chloride 0.9%, or Dextrose 5% Injection to a solution concentration of 2 mg per ml.

The reconstituted solution is stable at room temperature, in the vial or in a polypropylene (Terumo) syringe, in the presence or absence of light, for a period of 48 hours. However ,it is recommended that the solution be stored at 2-8°C in a refrigerator, and used within 24 hours, in line with good pharmaceutical practice.

7. Marketing Authorisation Holder

Faulding Pharmaceuticals Plc

Queensway

Royal Leamington Spa

Warwickshire CV31 3RW

United Kingdom

8. Marketing Authorisation Number(S)

PL 4515/0072 - 73

9. Date Of First Authorisation/Renewal Of The Authorisation

26^th July, 2001

10. Date Of Revision Of The Text

7^th December, 2000