ethinyl estradiol and desogestrel

Generic Name: ethinyl estradiol and desogestrel (EH thih nill ess tra DYE ole and des oh JESS trel)

Brand names: Apri, Cesia, Cyclessa, Desogen, Kariva, Mircette, Ortho-Cept, Reclipsen, Solia, Velivet, Azurette, Caziant, Emoquette

What is ethinyl estradiol and desogestrel?

Ethinyl estradiol and desogestrel contains a combination of female hormones that prevent ovulation (the release of an egg from an ovary). This medication also causes changes in your cervical mucus and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Ethinyl estradiol and desogestrel are used as contraception to prevent pregnancy.

Ethinyl estradiol and desogestrel may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about ethinyl estradiol and desogestrel?

Do not use birth control pills if you are pregnant or if you have recently had a baby. Do not use this medication if you have any of the following conditions: a history of stroke or blood clot, circulation problems (especially if caused by diabetes), a hormone-related cancer such as breast or uterine cancer, abnormal vaginal bleeding, liver disease or liver cancer, severe high blood pressure, migraine headaches, a heart valve disorder, or a history of jaundice caused by birth control pills.

You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions.

Taking hormones can increase your risk of blood clots, stroke, or heart attack, especially if you smoke and are older than 35.

Some drugs can make birth control pills less effective, which may result in pregnancy. Tell your doctor about all the prescription and over-the-counter medications you use, including vitamins, minerals and herbal products. Do not start using a new medication without telling your doctor.

What should I discuss with my healthcare provider before taking ethinyl estradiol and desogestrel?

This medication can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills (6 weeks if you are breast-feeding). Do not use this medication if you have:

• 
  

  a history of a stroke or blood clot;

  
  


• 
  

  circulation problems (especially if caused by diabetes);

  
  


• 
  

  a hormone-related cancer such as breast or uterine cancer;

  
  


• 
  

  abnormal vaginal bleeding;

  
  


• 
  

  liver disease or liver cancer;

  
  


• 
  

  severe high blood pressure;

  
  


• 
  

  severe migraine headaches;

  
  


• 
  

  a heart valve disorder; or

  
  


• 
  

  a history of jaundice caused by birth control pills.

  
  

Before using this medication, tell your doctor if you have any of the following conditions. You may need a dosage adjustment or special tests to safely take birth control pills.

• 
  

  high blood pressure, heart disease, congestive heart failure, angina (chest pain), or a history of heart attack;

  
  


• 
  

  high cholesterol or if you are overweight;

  
  


• 
  

  a history of depression;

  
  


• 
  

  gallbladder disease;

  
  


• 
  

  diabetes;

  
  


• 
  

  seizures or epilepsy;

  
  


• 
  

  a history of irregular menstrual cycles; or

  
  


• 
  

  a history of fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

  
  

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

How should I take ethinyl estradiol and desogestrel?

Take this medication exactly as it was prescribed for you. Do not take larger amounts, or take it for longer than recommended by your doctor. You will take your first pill on the first day of your period or on the first Sunday after your period begins (follow your doctor's instructions).

You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions.

The 28-day birth control pack contains seven "reminder" pills to keep you on your regular cycle. Your period will usually begin while you are using these reminder pills.

You may have breakthrough bleeding, especially during the first 3 months. Tell your doctor if this bleeding continues or is very heavy.

Take one pill every day, no more than 24 hours apart. When the pills run out, start a new pack the following day. You may get pregnant if you do not use this medication regularly. Get your prescription refilled before you run out of pills completely.

If you need to have any type of medical tests or surgery, or if you will be on bed rest, you may need to stop using this medication for a short time. Any doctor or surgeon who treats you should know that you are using birth control pills.

Your doctor will need to see you on a regular basis while you are using this medication. Do not miss any appointments.

Store this medication at room temperature away from moisture and heat.

See also: Ethinyl estradiol and desogestrel dosage (in more detail)

What happens if I miss a dose?

Missing a pill increases your risk of becoming pregnant. Follow the directions on the patient information sheet provided with your medicine. If you do not have an information sheet, call your doctor for instructions if you miss a dose.

If you miss one "active" pill, take two pills on the day that you remember. Then take one pill per day for the rest of the pack.

If you miss two "active" pills in a row in week one or two, take two pills per day for two days in a row. Then take one pill per day for the rest of the pack. Use back-up birth control for at least 7 days following the missed pills.

If you miss two "active" pills in a row in week 3, or if you miss three pills in a row during any of the first 3 weeks, throw out the rest of the pack and start a new one the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new one that day.

If you miss three "active" tablets in a row during any of the first 3 weeks, throw out the rest of the pack and start a new pack on the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new one that day.

If you miss two or more pills, you may not have a period during the month. If you miss a period for two months in a row, call your doctor because you might be pregnant.

If you miss any reminder pills, throw them away and keep taking one pill per day until the pack is empty. You do not need back-up birth control if you miss a reminder pill.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include nausea, vomiting, and vaginal bleeding.

What should I avoid while taking ethinyl estradiol and desogestrel?

Do not smoke while using this medication, especially if you are older than 35. Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills.

This medication will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

Ethinyl estradiol and desogestrel 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:

• 
  

  sudden numbness or weakness, especially on one side of the body;

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

  a change in the pattern or severity of migraine headaches;

  
  


• 
  

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

  
  


• 
  

  swelling in your hands, ankles, or feet;

  
  


• 
  

  a breast lump; or

  
  


• 
  

  symptoms of depression (sleep problems, weakness, mood changes).

  
  

Less serious side effects may include:

• 
  

  mild nausea, vomiting, bloating, stomach cramps;

  
  


• 
  

  breast pain, tenderness, or swelling;

  
  


• 
  

  freckles or darkening of facial skin;

  
  


• 
  

  increased hair growth, loss of scalp hair;

  
  


• 
  

  changes in weight or appetite;

  
  


• 
  

  problems with contact lenses;

  
  


• 
  

  vaginal itching or discharge;

  
  


• 
  

  changes in your menstrual periods, decreased sex drive; or

  
  


• 
  

  headache, nervousness, dizziness, tired feeling.

  
  

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.

Ethinyl estradiol and desogestrel Dosing Information

Usual Adult Dose for Contraception:

Desogestrel-ethinyl estradiol products are packaged in 21 or 28 day dosage preparations. The last seven tablets in 28 day dosage preparations are hormonally inert.

Regardless of the number of tablets in a package, the cycle length for oral contraceptives is generally considered to be 28 days. (The first day of menstrual bleeding is counted as day 1.)

Initiation of Oral Contraceptive Therapy

This product can be administered in two ways.

When initiating a Sunday start regimen, the first tablet may be taken on the first Sunday after menstruation begins. If a period begins on a Sunday, the first tablet may be taken on that day. When initiating a Sunday start regimen, another contraceptive method should be used until after the first 7 consecutive days of administration. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

When initiating a Day 1 start regimen, the first tablet is taken on the first day on menstruation. Such initiation may increase the risk of spotting and breakthrough bleeding but decrease the risk of early ovulation and pregnancy. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

Many clinicians recommend that additional contraceptive methods be used during the first cycle of hormonal therapy in order to reduce the risk of unintended pregnancy.

Missed Doses

If a woman misses one dose of active tablets, the missed dose should be taken as soon as it is remembered and the normal schedule should be resumed.

If a woman misses two doses in week 1 or week 2 of the cycle, 2 tablets may be taken as soon as they are remembered and 2 tablets taken the next day and the normal schedule may be resumed. (Additional contraceptive methods should be used for 7 days.)

If a woman misses two doses in week 3 or three doses at any time in the cycle, Day 1 starters should discard the current package and begin a new package that same day. Sunday starters should take 1 tablet daily from the current package until Sunday, when the current package is discarded and a new package begun. (Additional contraceptive methods should be used until the woman has taken at least 7 days of hormonal therapy from the new package.)

Usual Adult Dose for Abnormal Uterine Bleeding:

Desogestrel-ethinyl estradiol products are packaged in 21 or 28 day dosage preparations. The last seven tablets in 28 day dosage preparations are hormonally inert.

Regardless of the number of tablets in a package, the cycle length for oral contraceptives is generally considered to be 28 days. (The first day of menstrual bleeding is counted as day 1.)

This product can be administered in two ways.

When initiating a Sunday start regimen, the first tablet may be taken on the first Sunday after menstruation begins. If a period begins on a Sunday, the first tablet may be taken on that day. When initiating a Sunday start regimen, another contraceptive method should be used until after the first 7 consecutive days of administration. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

When initiating a Day 1 start regimen, the first tablet is taken on the first day on menstruation. Such initiation may increase the risk of spotting and breakthrough bleeding but decrease the risk of early ovulation and pregnancy. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

Missed Doses

If a woman misses one dose of active tablets, the missed dose should be taken as soon as it is remembered and the normal schedule should be resumed.

If a woman misses two doses in week 1 or week 2 of the cycle, 2 tablets may be taken as soon as they are remembered and 2 tablets taken the next day and the normal schedule may be resumed.

If a woman misses two doses in week 3 or three doses at any time in the cycle, Day 1 starters should discard the current package and begin a new package that same day. Sunday starters should take 1 tablet daily from the current package until Sunday, when the current package is discarded and a new package begun.

Usual Adult Dose for Endometriosis:

Desogestrel-ethinyl estradiol products are packaged in 21 or 28 day dosage preparations. The last seven tablets in 28 day dosage preparations are hormonally inert.

Regardless of the number of tablets in a package, the cycle length for oral contraceptives is generally considered to be 28 days. (The first day of menstrual bleeding is counted as day 1.)

This product can be administered in two ways.

When initiating a Sunday start regimen, the first tablet may be taken on the first Sunday after menstruation begins. If a period begins on a Sunday, the first tablet may be taken on that day. When initiating a Sunday start regimen, another contraceptive method should be used until after the first 7 consecutive days of administration. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

When initiating a Day 1 start regimen, the first tablet is taken on the first day on menstruation. Such initiation may increase the risk of spotting and breakthrough bleeding but decrease the risk of early ovulation and pregnancy. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

Missed Doses

If a woman misses one dose of active tablets, the missed dose should be taken as soon as it is remembered and the normal schedule should be resumed.

If a woman misses two doses in week 1 or week 2 of the cycle, 2 tablets may be taken as soon as they are remembered and 2 tablets taken the next day and the normal schedule may be resumed.

If a woman misses two doses in week 3 or three doses at any time in the cycle, Day 1 starters should discard the current package and begin a new package that same day. Sunday starters should take 1 tablet daily from the current package until Sunday, when the current package is discarded and a new package begun.

Usual Adult Dose for Gonadotropin Inhibition:

Desogestrel-ethinyl estradiol products are packaged in 21 or 28 day dosage preparations. The last seven tablets in 28 day dosage preparations are hormonally inert.

Regardless of the number of tablets in a package, the cycle length for oral contraceptives is generally considered to be 28 days. (The first day of menstrual bleeding is counted as day 1.)

This product can be administered in two ways.

When initiating a Sunday start regimen, the first tablet may be taken on the first Sunday after menstruation begins. If a period begins on a Sunday, the first tablet may be taken on that day. When initiating a Sunday start regimen, another contraceptive method should be used until after the first 7 consecutive days of administration. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

When initiating a Day 1 start regimen, the first tablet is taken on the first day on menstruation. Such initiation may increase the risk of spotting and breakthrough bleeding but decrease the risk of early ovulation and pregnancy. For a 28 day package, one tablet is taken daily for 28 days and a new package begun on the following day. For a 21 day package, one tablet is taken daily for 21 days followed by 7 days with no medication. A new package of contraceptives is begun on the following day.

Missed Doses

If a woman misses one dose of active tablets, the missed dose should be taken as soon as it is remembered and the normal schedule should be resumed.

If a woman misses two doses in week 1 or week 2 of the cycle, 2 tablets may be taken as soon as they are remembered and 2 tablets taken the next day and the normal schedule may be resumed.

If a woman misses two doses in week 3 or three doses at any time in the cycle, Day 1 starters should discard the current package and begin a new package that same day. Sunday starters should take 1 tablet daily from the current package until Sunday, when the current package is discarded and a new package begun.

What other drugs will affect ethinyl estradiol and desogestrel?

Some drugs can make birth control pills less effective, which may result in pregnancy. Before using this medication, tell your doctor if you are using any of the following drugs:

• 
  

  acetaminophen (Tylenol) or ascorbic acid (vitamin C);

  
  


• 
  

  an antibiotic;

  
  


• 
  

  phenylbutazone (Azolid, Butazolidin);

  
  


• 
  

  St. John's wort;

  
  


• 
  

  seizure medicines such as phenytoin (Dilantin), carbamazepine (Tegretol), topiramate (Topamax), and others;

  
  


• 
  

  a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or

  
  


• 
  

  HIV medicines such as amprenavir (Agenerase), atazanavir (Reyataz), indinavir (Crixivan), saquinavir (Invirase), fosamprenavir (Lexiva), ritonavir (Norvir), and others.

  
  

This list is not complete and there may be other drugs that can affect birth control pills. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More ethinyl estradiol and desogestrel resources

• Ethinyl estradiol and desogestrel Side Effects (in more detail)
• Ethinyl estradiol and desogestrel Dosage
• Ethinyl estradiol and desogestrel Use in Pregnancy & Breastfeeding
• Ethinyl estradiol and desogestrel Drug Interactions
• Ethinyl estradiol and desogestrel Support Group
• 162 Reviews for Ethinyl estradiol and desogestrel - Add your own review/rating

Compare ethinyl estradiol and desogestrel with other medications

• Abnormal Uterine Bleeding
• Birth Control
• Endometriosis
• Gonadotropin Inhibition
• Polycystic Ovary Syndrome

Where can I get more information?

• Your pharmacist can provide more information about ethinyl estradiol and desogestrel.

See also: ethinyl estradiol and desogestrel side effects (in more detail)

Sal-Tropine

Generic Name: atropine (AT roe peen)

Brand Names: Atreza, Sal-Tropine

What is Sal-Tropine (atropine)?

Atropine produces many effects in the body, including relief from spasms of the gastrointestinal tract (stomach and intestines), the bladder, and the biliary tract. This is helpful in controlling conditions such as colitis, spastic bladder, diverticulitis, infant colic, renal and biliary colic, peptic ulcer, and irritable bowel syndrome.

Atropine also reduces the secretions of many organs, thereby helping to control conditions such as excessive stomach acid production and excessive secretion from the pancreas; to reduce secretions of the nose, lungs, salivary glands, and stomach before surgery; and to help dry up excessive mucus production associated with diseases, infections, and allergies.

Atropine is used to treat the rigidity, tremor, excessive salivation, and sweating caused by Parkinson's disease.

Atropine also has effects on the heart. It is used during surgery to maintain proper heart function, during emergencies involving the heart, and to treat certain heart disorders.

Atropine is used to control laughing and crying episodes that are caused by brain tumors.

Atropine also has effect on the eyes and is available in an ophthalmic (eye) formulation.

Atropine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Sal-Tropine (atropine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Atropine may cause dizziness, drowsiness, or blurred vision. If you experience dizziness, drowsiness, or blurred vision, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking atropine.

Avoid becoming overheated in hot weather. Atropine increases the risk of heat stroke because it causes decreased sweating.

What should I discuss with my healthcare provider before taking Sal-Tropine (atropine)?

Do not take atropine if you have

• kidney disease;


• 
  

  a blockage of your urinary tract (difficulty urinating);

  
  


• 
  

  a blockage in your intestines, severe ulcerative colitis, or ulcerative colitis complicated by toxic megacolon;

  
  


• 
  

  glaucoma; or

  
  


• 
  

  myasthenia gravis.

  
  

Before taking this medication, tell your doctor if you have

• 
  

  numbness or tingling in your hands or feet;

  
  


• liver disease;


• 
  

  ulcerative colitis;

  
  


• 
  

  thyroid problems;

  
  


• 
  

  high blood pressure, an irregular heartbeat, or any type of heart disease;

  
  


• 
  

  hiatal hernia or reflux disease;

  
  


• 
  

  enlargement of the prostate; or

  
  


• 
  

  asthma, chronic lung disease, or allergies.

  
  

You may not be able to take atropine, or you may require a lower dose or special monitoring during treatment if you have any of the conditions listed above.

It is not known whether atropine will harm an unborn baby. Do not take atropine without first talking to your doctor if you are pregnant. It is not known whether atropine passes into breast milk. Do not take atropine without first talking to your doctor if you are breast-feeding a baby.

How should I take Sal-Tropine (atropine)?

Take atropine exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water. Store atropine at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of a atropine overdose include headache; nausea; vomiting; dry mouth; difficulty swallowing; blurred vision; dilated pupils; hot, dry skin; dizziness; drowsiness; confusion; anxiety; seizures; weak pulse; and an irregular heartbeat.

What should I avoid while taking Sal-Tropine (atropine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Atropine may cause dizziness, drowsiness, or blurred vision. If you experience dizziness, drowsiness, or blurred vision, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking atropine.

Avoid becoming overheated in hot weather. Atropine increases the risk of heat stroke because it causes decreased sweating.

Sal-Tropine (atropine) side effects

If you experience any of the following serious side effects, stop taking atropine and seek emergency medical attention:

• 
  

  an allergic reaction (swelling of your lips, tongue, or face, difficulty breathing, closing of your throat, or hives);

  
  


• 
  

  an irregular or fast heart rate;

  
  


• 
  

  rash or flushing; or

  
  


• 
  

  eye pain.

  
  

Other, less serious side effects may be more likely to occur. Continue to take atropine and talk to your doctor if you experience

• 
  

  headache, dizziness or lightheadedness;

  
  


• 
  

  weakness or nervousness;

  
  


• 
  

  blurred vision, large pupils, or sensitivity of the eyes to bright light;

  
  


• 
  

  nausea, bloating, heartburn, or constipation;

  
  


• 
  

  changes in taste;

  
  


• 
  

  difficulty urinating;

  
  


• 
  

  decreased sweating; or

  
  


• 
  

  nasal congestion, stuffiness, or a dry mouth.

  
  

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 Sal-Tropine (atropine)?

Many other drugs may increase the side effects of atropine. Before taking this medication, tell your doctor if you are taking any of the following medicines:

• 
  

  belladonna (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), methscopolamine (Pamine), or scopolamine (Transderm-Scop);

  
  


• 
  

  bronchodilators such as ipratropium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  digoxin (digitalis, Lanoxin);

  
  


• 
  

  glycopyrrolate (Robinul);

  
  


• 
  

  mepenzolate (Cantil);

  
  


• 
  

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

  
  


• 
  

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

  
  

Drugs other than those listed here may also interact with atropine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More Sal-Tropine resources

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

• Sal-Tropine MedFacts Consumer Leaflet (Wolters Kluwer)


• Atropine Prescribing Information (FDA)


• Atropine Professional Patient Advice (Wolters Kluwer)


• Atropine Monograph (AHFS DI)


• Atropine MedFacts Consumer Leaflet (Wolters Kluwer)


• Atropine Advanced Consumer (Micromedex) - Includes Dosage Information


• AtroPen Prescribing Information (FDA)

Compare Sal-Tropine with other medications

• Anticholinesterase Poisoning
• AV Heart Block
• Bradyarrhythmia

Where can I get more information?

• Your pharmacist can provide more information about atropine.

See also: Sal-Tropine side effects (in more detail)

Anidulafungin

Pronunciation: ay-NID-ue-la-FUN-jin
Generic Name: Anidulafungin
Brand Name: Eraxis

Anidulafungin is used for:

Treating certain types of fungal infections.

Anidulafungin is an echinocandin antifungal. It works by killing sensitive fungi.

Do NOT use Anidulafungin if:

• you are allergic to any ingredient in Anidulafungin or to another echinocandin antifungal (eg, caspofungin)

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

Before using Anidulafungin:

Some medical conditions may interact with Anidulafungin. 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

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

Ask your health care provider if Anidulafungin 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 Anidulafungin:

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

• Anidulafungin is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Anidulafungin at home, a health care provider will teach you how to use it. Be sure you understand how to use Anidulafungin. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.


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


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


• To clear up your infection completely, use Anidulafungin for the full course of treatment. Keep using it even if you feel better in a few days.


• If you miss a dose of Anidulafungin, use 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 use 2 doses at once.

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

Important safety information:

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


• Anidulafungin only works against fungi; it does not treat viral infections (eg, the common cold).


• Be sure to use Anidulafungin for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The fungus could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.


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


• Anidulafungin should be used with extreme caution in CHILDREN; safety and effectiveness in 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 Anidulafungin while you are pregnant. It is not known if Anidulafungin is found in breast milk. If you are or will be breast-feeding while you use Anidulafungin, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Anidulafungin:

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:

Diarrhea; flushing; headache.

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); dark urine; fainting; fever, chills, or persistent sore throat; irregular heartbeat; leg or calf redness, swelling, or pain; muscle pain, weakness, or cramping; pain, swelling, or redness at the injection site; pale stools; seizures; severe or persistent dizziness or stomach pain; shortness of breath; unusual bruising or bleeding; vision problems (eg, blurred vision); wheezing; 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: Anidulafungin side effects (in more detail)

If OVERDOSE is suspected:

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

Proper storage of Anidulafungin:

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

General information:

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


• Anidulafungin 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 Anidulafungin. 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 Anidulafungin resources

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

• Anidulafungin Professional Patient Advice (Wolters Kluwer)


• Anidulafungin Monograph (AHFS DI)


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


• Eraxis Prescribing Information (FDA)


• Eraxis Consumer Overview

Compare Anidulafungin with other medications

• Candida Infections, Systemic
• Esophageal Candidiasis

Zylet

Generic Name: loteprednol and tobramycin (Ophthalmic route)

loe-te-PRED-nol et-a-BOE-nate, toe-bra-MYE-sin

Commonly used brand name(s)

In the U.S.

• Zylet

Available Dosage Forms:

• Suspension

Therapeutic Class: Aminoglycoside/Corticosteroid Combination

Pharmacologic Class: Loteprednol

Chemical Class: Aminoglycoside

Uses For Zylet

Loteprednol and tobramycin ophthalmic (eye) solution or drops is used to treat inflammation or swelling in the eye that is caused by a bacterial infection.

Loteprednol and tobramycin solution is a combination of a steroid (loteprednol) and an antibiotic (tobramycin). Loteprednol reduces swelling and inflammation. Tobramycin works by killing the bacteria or preventing it from growing.

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

Before Using Zylet

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of loteprednol and tobramycin eye drops in the pediatric population. 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 loteprednol and tobramycin eye drops in the elderly.

Pregnancy

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

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. 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:

• Cataract surgery, recent or


• Cornea (part of the eye) problems, history of or


• Sclera (part of the eye) problems, history of—May cause side effects to become worse.

• Fungal (caused by a fungus) eye infection or


• Herpes simplex eye infection or


• Smallpox eye infection or


• Tuberculosis eye infection or


• Varicella (chickenpox) eye infection or


• Viral (caused by a virus) eye infection—Should not be used in patients with these conditions.

• Glaucoma, history of—Use with caution. May make this condition worse.

Proper Use of Zylet

Your eye doctor will tell you how much of this medicine to use and how often. Do not use more medicine or use it more often than your doctor tells you to. This medicine is not for long-term use.

To help clear up your eye infection completely, keep using this medicine for the full time of treatment, even if your eye feels better.

If you normally wear soft contact lenses, remove them while you are using this medicine. Talk to your eye doctor about this if you have questions.

To use the eye drops:

• Wash your hands with soap and water.


• Shake the bottle well before taking the top off and before each dose.


• For the first dose, make sure the imprinted neckband is on the bottle and holding the top in place.


• Tilt your head back and, pressing your finger gently on the skin just beneath the lower eyelid, pull the eyelid away from the eye to make a space. Drop the medicine into this space.


• Let go of the eyelid and gently close the eye. Do not blink. Keep the eye closed for 1 or 2 minutes to allow the medicine to cover the eye.


• If you think you did not get the drop of medicine into your eye properly, repeat the process with another drop.


• Wash your hands after using the eye drops to remove any medicine.


• Never touch the applicator tip to any surface, including the eye, and keep the container tightly closed. This will keep the medicine as germ-free as possible.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For ophthalmic dosage form (eye drops):
  
  • For eye infections:
    
    • Adults—Use one or two drops in the affected eye every 4 to 6 hours. Your doctor may tell you to use the drops more often during the first two days for serious infections.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using Zylet

If you will be using this medicine for more than a few weeks, your eye doctor will check your eyes at regular visits to make sure it is working properly and is not causing unwanted effects.

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

Zylet Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

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

More common

• Blurred vision


• change in vision


• feeling like something is in the eye


• increased intraocular pressure


• loss of vision


• pain or irritation of the clear front part of the eye


• sensitivity of the eyes to light

Less common

• Blurred vision or seeing blue-green halos around objects


• decreased vision


• difficulty seeing at night


• discharge from the eye


• dry eyes


• eyelid burning, redness, itching, pain, or tenderness


• fast heartbeat


• fever


• hives


• hoarseness


• irritation and swelling of the eye


• itching


• joint pain


• lid itching and swelling


• pain in the eye


• rash


• redness of the eyelid


• redness of the skin


• shortness of breath


• stiffness or swelling


• swelling of the eyelids, face, lips, hands, or feet


• tightness in the chest


• troubled breathing or swallowing


• wheezing

Incidence not known

• Redness of the eye


• tearing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Burning of the eye


• headache


• increased sensitivity of the eyes to light


• stinging of the eye

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: Zylet side effects (in more detail)

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

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

More Zylet resources

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

• Zylet Prescribing Information (FDA)


• Zylet Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Zylet Consumer Overview

Compare Zylet with other medications

• Conjunctivitis, Bacterial
• Cyclitis
• Iritis
• Keratitis
• Uveitis

Perindopril Tablets

Perindopril 2mg, 4mg and 8mg Tablets

Perindopril tert-butylamine

Read all of this leaflet carefully before you start taking this medicine

• Keep this leaflet. You may need to read it again.


• If you have any further questions, consult your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others.
  
  It may harm them, even if their symptoms are the same as yours.


• If any of the side effects becomes serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What are Perindopril tablets and what they are used for?


• 2. What you should know before you take Perindopril tablets.


• 3. How is Perindopril tablets taken?


• 4. Possible side effects.


• 5. How to store Perindopril tablets.


• 6. Further information.

What are Perindopril tablets and what they are used for

Perindopril belongs to a group of medicines called ACE inhibitors. These work by widening the blood vessels. This makes it easier for your heart to pump blood through the body.

Perindopril 2mg or 4mg tablets are used to:

• treat high blood pressure (hypertension)


• treat heart failure (a condition where the heart is unable to pump enough blood to meet the body’s needs)


• reduce the risk of cardiac events, such as heart attack, in patients with stable coronary artery disease (a condition where the blood supply to the heart is reduced or blocked) and who have already had a heart attack and/or an operation to improve the blood supply to the heart by widening the vessels that supply it.

Perindopril 8mg tablets are used to:

• treat high blood pressure (hypertension)


• reduce the risk of cardiac events, such as heart attack, in patients with stable coronary artery disease (a condition where the blood supply to the heart is reduced or blocked) and who have already had a heart attack and/or an operation to improve the blood supply to the heart by widening the vessels that supply it.

Before you take Perindopril tablets

Do not take Perindopril tablets:

• If you are allergic (hypersensitive) to perindopril or to any of the other ingredients of Perindopril tablets or to any other ACE inhibitor (see Further Information, section 6),


• if you have in the past suffered from acute swelling of the face, tongue or larynx (angioneurotic syndrome), regardless of whether or not it has been caused by treatment with a similar medicine (ACE inhibitor).


• If you are more than 3 months pregnant. (it is also better to avoid Perindopril tablets in early pregnancy (see pregnancy section).

Children

Perindopril tablets are not for use in children.

Take special care with Perindopril tablets

Talk to your doctor before taking Perindopril tablets if:

• you have narrowing of the heart valves (aortic or mitral stenosis) or heart muscle disease (hypertrophic cardiomyopathy) or narrowing of the artery supplying the kidney with blood (renal artery stenosis)


• if you have recently had a kidney transplant


• you have any other heart or liver or kidney problems, or if you are having dialysis


• you have diabetes which is not well controlled


• you have been told to limit the salt in your diet or to use a salt-substitute containing potassium


• you have a collagen disease such as systemic lupus erythematosus or scleroderma.


• you are going to have or are having treatment to reduce the effects of an allergy to bee or wasp stings


• you are going to have cholesterol removed from your blood by a machine (LDL apheresis).


• You must tell your doctor if you think you are (or might become) pregnant.
  
  Perindopril tablets are not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after that stage (see pregnancy section).

In the event of the occurrence of a feeling of tightness in the chest and swelling of the face and tongue (angioneurotic oedema), you should immediately notify your doctor and stop the treatment with Perindopril tablets 2mg, 4mg or 8mg. This applies to all ACE inhibitors.

Tell the doctor or pharmacist that you are taking Perindopril tert-butylamine if:

• you are about to have an operation or a general anaesthetic


• you have recently had diarrhoea or vomited


• your blood pressure is not sufficiently lowered due to ethnic affiliation
  
  (particularly in patients with black skin colour)

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

In particular, talk to your doctor before taking Perindopril tert-butylamine if you are taking:

• medicines for high blood pressure including water tablets (diuretics)


• water tablets (diuretics) which affect potassium, such as spironolactone, triamterene or amiloride


• medicines to increase your level of potassium


• heparin (for thinning the blood) can also affect potassium levels in your blood


• medicines for diabetes (insulin or tablets)


• lithium (for mania or depression)


• medicines for mental illness such as depression, anxiety, schizophrenia or other psychosis


• allopurinol for gout


• medicines to treat auto-immune disorders (such as rheumatoid arthritis) or given after transplant surgery. These are called immunosupressants.


• procainamide (for irregular heartbeat)


• non-steroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, diclofenac), including aspirin for pain


• medicines for low blood pressure, shock or asthma (including ephedrine, noradrenaline or adrenaline)


• medicines that make the blood vessels wider (vasodilators, such as nitrates).

Ask your doctor if you are not sure what these medicines are. Tell the doctor if you have taken any of the medicines listed above in the past, but have now stopped.

Taking Perindopril tablets with food and drink

It is recommended to take Perindopril tablets in the morning before a meal to reduce the influence of food on the way in which the medicine works. Potassium containing food additives or salt substitutes should not be used if you use Perindopril.

Pregnancy and Breastfeeding:

Ask your doctor or pharmacist for advice before taking any medicine

Pregnancy:

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop taking Perindopril tablets before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Perindopril tablets. Perindopril tablets are not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding:

Tell your doctor if you are breast-feeding or about to start breast-feeding. Perindopril tablets are not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.

Driving and using machines

You may feel dizzy or tired when taking Perindopril tert-butylamine, just as with other ACE inhibitors. If this happens, do not drive or use machines. You must talk to your doctor about this

Important information about some of the ingredients of Perindopril tablets

The tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine

How to take Perindopril tablets

Your doctor will decide on the amount of perindopril tert-butylamine you should start to take. This may be increased depending on your condition and other medicines you are taking. Always take Perindopril tert-butylamine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. Do not change the amount of medicine you take unless your doctor tells you. Perindopril tert-butylamine may be used on its own, or with other medicines which lower blood pressure.

• Take Perindopril tablets by mouth only.


• Take them in the morning, before a meal.


• It is best to take your tablet(s) with a glass of water at the same time each day.

Perindopril tert-butylamine is not for use in children.

The usual dose is:

High blood pressure:

• Starting dose - 4mg Perindopril tert-butylamine each day


• after a month, this may be raised to 8mg each day.
  
  8mg each day is the highest amount normally used.

In older people with high blood pressure the daily amounts are usually:

• 2mg each day


• after a month, this may be raised to 4mg each day.
  
  8mg each day is the highest amount used.

Perindopril tert-butylamine 2mg, 4mg or 8mg should only be used with other medicines for high blood pressure which are not also ACE inhibitors.

If you are taking water tablets (diuretics):

• your doctor may stop them 2 to 3 days before you start taking Perindopril tert-butylamine. This is to prevent a fall in your blood pressure.


• if needed, you can start taking water tablets again after you have started Perindopril tert-butylamine.


• if it is not possible to stop your water tablets, then you can take 2mg of perindopril tert-butylamine as well.

Your doctor or pharmacist will tell you exactly what you should do.

The doctor may start you with 2mg perindopril tert-butylamine if:

• your blood pressure is very high


• you do not have enough water in your body (dehydrated).


• you have a low level of salt in your blood.


• you have a heart problem which means that it has difficulty in pumping blood through the body (cardiac decompensation).


• you have high blood pressure due to the blood vessels in the kidneys being blocked (constriction of the arteries).


• you have an excessive drop in blood pressure following the initial dose.

Heart failure:

The 8mg strength is not suitable for treatment of this condition.

• Starting dose 2mg Perindopril tert-butylamine each day.


• after 2 weeks, this may be raised to 4mg each day.

Stable coronary artery disease:

• the usual starting dose is 4mg Perindopril tert-butylamine once daily


• after two weeks, this may be raised to 8mg each day.

In older people with stable coronary artery disease the daily amounts are usually:

• 2mg each day


• after one week, this may be raised to 4mg each day


• and after a further week to 8mg each day which is the highest amount used.

If you take more perindopril tert-butylamine than you should

Immediately contact your doctor if you have taken too high a dose.

The following effects may happen: low blood pressure, shock, kidney problems, fast breathing, fast heartbeat, uneven heartbeat (palpitations), slow heartbeat, feeling dizzy or anxious and cough.

If you forget to take perindopril tert-butylamine

Do not take a double dose to make up for a forgotten dose.

If you have forgotten to take one or more tablets, you should skip the tablets which you have forgotten. Contact your doctor if in doubt.

If you stop taking perindopril tert-butylamine

Do not stop taking Perindopril tablets without talking to your doctor.

Medicines for high blood pressure or heart failure will normally have to be taken for the rest of your life. If you stop taking Perindopril tablets your condition may get worse.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Perindopril Tablets Side Effects

Like all medicines, perindopril tert-butylamine can cause side effects, although not everyone gets them.

If any of the following effects happen, stop taking your tablets and tell your doctor immediately:

• swelling of the face, lips, mouth, tongue or throat


• difficulty in breathing


• feeling dizzy or faint


• very fast or uneven heartbeat.

This is a very rare but serious reaction called angioedema, which can happen with all medicines of this type (ACE inhibitors). You must get treatment immediately, usually in hospital.

Common (affecting 1 or more than 1 in 100 but less than 1 in 10 patients)

• cough, shortness of breath


• feeling faint due to low blood pressure (especially when you start Perindopril tert-butylamine, or when the amount is increased, or when you also take water tablets)


• headache, feeling dizzy or tired, feeling dizzy with a spinning sensation (vertigo), pins and needles, muscle cramps, blurred vision, eye pain, sensation of noises in the ears (tinnitus)


• feeling or being sick, stomach pain or indigestion,


• changes in your sense of taste, diarrhoea, constipation, skin rash, itching.

Uncommon (affecting 1 or more than 1 in 1000 but less than 1 in 100 patients)

• changes in mood or sleep


• tight feeling in the chest, wheezing and short of breath (bronchospasm)


• dry mouth


• kidney problems


• unable to get an erection


• sweating


• wheezing, swelling of the face, tongue or throat, intense itching, skin rash, fainting or feeling dizzy (angioedema).

Very rare (affecting less than 1 in 10,000 patients)

• feeling confused


• uneven heartbeat, chest pain that happens in heart disease (angina), heart attack and stroke (these have happened with ACE inhibitors in people with low blood pressure)


• chest infection (eosinophilic pneumonia), blocked up or runny nose (rhinitis)


• inflamed pancreas (pancreatitis)


• inflamed liver (hepatitis)


• skin reaction like an allergy (erythema multiforme)


• changes in the blood. Your doctor may carry out blood tests to check for this.


• acute kidney problems

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Perindopril tablets

• Keep out of the reach and sight of children.


• Do not store above 30°C.

Do not use Perindopril tablets after the expiry date which appears on the packet after “do not use after” or “exp”. The first 2 figures show the month, while the last figures show the year.

Medicines should not be disposed of via wastewater or in the household refuse. Ask your pharmacist what you should do with medicines which are no longer required. These measures will help to protect the environment.

Further information

What Perindopril tablets contains

The active substance is: perindopril tert-butylamine.

Each Perindopril 2mg tablet contains 2mg of perindopril tert-butylamine salt equivalent to 1.669mg of perindopril.

Each Perindopril 4mg tablet contains 4mg of perindopril tert-butylamine salt equivalent to 3.338mg of perindopril.

Each Perindopril Tablets 8mg tablet contains 8mg of perindopril tert-butylamine salt equivalent to 6.676mg perindopril.

Other ingredients (excipients) are:

Hydrophobic colloidal silica, microcrystalline cellulose, lactose and magnesium stearate.

What Perindopril tablets looks like and contents of the pack

2 mg: White, round, biconvex tablets, plain on both sides.

4 mg: White, oblong tablets with a break line on both sides, ‘PP’ on one side and ‘4’ on the other.

8 mg: White, round, biconvex tablets with ‘PP’ on one side and ‘8’ on the other.

Each strength of tablet is available in packaging containing 14, 20, 28, 30, 56, 60 and 90 tablets in alu-alu blister packaging.

Not all pack sizes may be marketed.

Marketing Authorisation holder and Manufacturer

Marketing Authorisation holder

Actavis Group PTC ehf

Reykjavikurvegur 76-78

220 Hafnarfjordur

Iceland

Manufacturers

Tillomed Laboratories Ltd

3 Howard Road

Eaton Socon

St Neots

Cambridgeshire

PE19 3ET

United Kingdom

Medicamenta a.s.

Bělohorská 39/260

169 00 Prague 6

Czech Republic

Actavis BV

Baarnsche Dijk 1

3741 LN Baarn

The Netherlands

This leaflet was last approved in June 2009

Actavis

Barnstaple

EX32 8NS

UK

GLEPL003

Imdur Tablets 60mg

IMDUR


TABLETS 60mg

isosorbide mononitrate

What you should know about Imdur Tablets 60 mg isosorbide mononitrate

Please read this leaflet carefully before you take your medicine.

If you have any questions or are unsure about anything to do with your medicine ask your doctor or pharmacist (chemist). Remember, this medicine is only for you. Never give it to anyone else even if their symptoms are similar to yours.

Each tablet contains 60 mg of the active ingredient isosorbide mononitrate in an extended-release formulation based on Durules.

Each tablet also contains the following inactive ingredients: aluminium silicate, paraffin special, hydroxypropylcellulose, magnesium stearate, colloidal anhydrous silica, hypromellose, macrogol, titanium dioxide and iron oxide.

The tablets are made so that they release the medicine slowly over a number of hours.

Imdur Tablets 60 mg come in blister strips containing 7 tablets, which have the days of the week shown. A pack may contain either 7, 14, 28 or 98 tablets as multiples of the 7 tablet blister strip. Imdur Tablets 60 mg may also come in glass bottles of 100 tablets.

Imdur is a type of medicine called a nitrate.

Who has made your medicine?

The Marketing Authorisation for Imdur Tablets 60 mg is held by

AstraZeneca UK Limited

600 Capability Green

Luton

LU1 3LU

UK

Imdur Tablets 60 mg are manufactured by

AstraZeneca UK Limited

Silk Road Business Park

Macclesfield

Cheshire

SK10 2NA

UK

What is your medicine used for?

Imdur Tablets 60 mg can help prevent an attack of angina (chest pain).

Before taking your medicine

The questions below are to check that it is safe for you to take this medicine. If you can answer yes to any of these, you should discuss it with your doctor or pharmacist before taking the medicine.

• Have you ever had an allergic reaction to these tablets or any of their ingredients?


• Have you ever had a stroke?


• Do you suffer from low blood pressure (hypotension)?


• Are you pregnant, think you might be pregnant, or considering becoming pregnant?


• Are you breast-feeding?


• Do you suffer from severe anaemia?


• Have you ever had any serious damage to your heart, such as a heart attack or operation?


• Do you suffer from the heart conditions cardiomyopathy or pericarditis or have narrow heart valves?


• Are you taking a medicine called a Phosphodiesterase Type 5 Inhibitor? Examples of this type of medicine are Viagra (sildenafil), Cialis (tadalafil), and Levitra (vardenafil).

You must not use Imdur Tablets 60 mg for the relief of sudden (acute) attacks of angina. In the event of a sudden attack you should take a glyceryl trinitrate tablet (always follow the instructions given on the label).

Driving and using machines

You may experience dizziness when you start taking Imdur Tablets 60 mg. You should therefore know how you react to Imdur Tablets 60 mg before you drive or use machines.

Taking other medicines

Do not take Imdur Tablets 60 mg and Phosphodiesterase Type 5 Inhibitors, such as Viagra (sildenafil), Cialis (tadalafil), or Levitra (vardenafil), at the same time as you may experience serious side effects.

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those not prescribed.

Taking your medicine

If you have been prescribed these tablets by your doctor you should follow the instructions they have given you. The usual dose is one or sometimes two tablets a day taken in the morning. If you are taking two tablets a day, please ensure you take one tablet from each blister strip marked with the same day of the week. These tablets should not be given to children.

The tablets may be swallowed whole or broken in half if this is easier and swallowed with half a glass of water. They should not be chewed or crushed.

Very occasionally, some people find that the tablet appears in their bowel motions (faeces). This is quite normal and does not mean that the medicine has not been released.

What happens if you take too many?

If you take too many tablets, contact your doctor or pharmacist straight away.

What to do if you forget to take a dose?

If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, do not take the missed dose, just take the next dose on time.

After taking your medicine

Like all medicines Imdur Tablets 60 mg may sometimes cause side effects, as well as the effects that are needed.

Some people may suffer from headaches, nausea or dizziness while taking Imdur Tablets but these problems usually disappear with time. Rarely you may experience a rash or itching. Very rarely you may experience muscle pain.

If you suffer from any of these, or if you get any other unusual or unexpected symptoms, talk to your doctor or pharmacist (chemist).

Storing your medicine

• Do not take your tablets after the expiry date shown on the carton and blister strip.


• Store out of the reach and sight of children.


• Keep this medicine below 30°C.


• Remember to return any unused medicine to your pharmacist (chemist).

Leaflet updated: February 2007

© AstraZeneca 2007

Imdur is a trade mark of the AstraZeneca group of companies.

X CV 05 0302

P020871

Ondansetron 2mg / ml Solution for Injection (Wockhardt UK Ltd)

1. Name Of The Medicinal Product

Ondansetron 2mg/ml Solution for Injection or Infusion

2. Qualitative And Quantitative Composition

Each ml contains 2mg of ondansetron (as hydrochloride dihydrate)

Each 2ml ampoule contains 4mg of ondansetron (as hydrochloride dihydrate)

Each 4ml ampoule contains 8mg of ondansetron (as hydrochloride dihydrate)

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Solution for injection or infusion

Clear, colourless solution, free from particles.

4. Clinical Particulars

4.1 Therapeutic Indications

Adults

Ondansetron hydrochloride is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy, and for the prevention and treatment of post-operative nausea and vomiting (PONV).

Paediatric Population

Ondansetron hydrochloride is indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in children aged

4.2 Posology And Method Of Administration

Chemotherapy and Radiotherapy

For intravenous use or for intramuscular use. Refer to Section 6.6 'Instructions for Use and Handling', for information on compatibility with intravenous fluids and other drugs.

For single use. Discard any unused product immediately after use

Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of Ondansetron hydrochloride should be flexible in the range of 8-32mg a day and selected as shown below.

Emetogenic chemotherapy and radiotherapy: Ondansetron hydrochloride can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular administration.

For most patients receiving emetogenic chemotherapy or radiotherapy, Ondansetron hydrochloride 8mg should be administered as a slow intravenous or intramuscular injection immediately before treatment, followed by 8 mg orally twelve hourly.

To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with Ondansetron hydrochloride should be continued for up to five days after a course of treatment.

Highly emetogenic chemotherapy: For patients receiving highly emetogenic chemotherapy, e.g. high-dose cisplatin, Ondansetron hydrochloride can be given either by rectal, intravenous or intramuscular administration.

Ondansetron hydrochloride has been shown to be equally effective in the following dose schedules over the first 24 hours of chemotherapy:

- A single dose of 8mg by slow intravenous or intramuscular injection immediately before chemotherapy.

- A dose of 8mg by slow intravenous or intramuscular injection immediately before chemotherapy, followed by two further intravenous or intramuscular doses of 8mg two to four hours apart, or by a constant infusion of 1mg/hour for up to 24 hours.

- A single dose of 32mg diluted in 50-l00ml of saline or other compatible infusion fluid (see Pharmaceutical Precautions) and infused over not less than 15 minutes immediately before chemotherapy.

The selection of dose regimen should be determined by the severity of the emetogenic challenge.

The efficacy of ondansetron hydrochloride in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20mg administered prior to chemotherapy.

To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron hydrochloride should be continued for up to five days after a course of treatment.

Paediatric Population

CINV in children aged

The dose for CINV can be calculated based on body surface area (BSA) or weight – see below. Weight-based dosing results in higher total daily doses compared to BSA-based dosing (sections 4.4.and 5.1).

Ondansetron hydrochloride should be diluted in 5% dextrose or 0.9% sodium chloride or other compatible infusion fluid (see section 6.6) and infused intravenously over not less than 15 minutes.

There are no data from controlled clinical trials on the use of ondansetron hydrochloride in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of ondansetron hydrochloride for radiotherapy-induced nausea and vomiting in children.

Dosing by BSA

Ondansetron hydrochloride should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m². The intravenous dose must not exceed 8 mg.

Oral dosing can commence twelve hours later and may be continued for up to 5 days (Table 1).

The total daily dose must not exceed adult dose of 32 mg.

Table 1: BSA-based dosing for Chemotherapy - Children aged

BSA	Day 1 (a,b)	Days 2-6 (b)
<0.6m2	5 mg/m2 i.v. plus 2 mg syrup after 12 hrs	2 mg syrup every 12 hrs
2	5 mg/m2 i.v. plus 4 mg syrup or tablet after 12 hrs	4 mg syrup or tablet every 12 hrs

a The intravenous dose must not exceed 8mg.

b The total daily dose must not exceed adult dose of 32 mg

Dosing by bodyweight

Weight-based dosing results in higher total daily doses compared to BSA-based dosing (sections 4.4. and 5.1).

Ondansetron hydrochloride should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The intravenous dose must not exceed 8 mg.

Two further intravenous doses may be given in 4-hourly intervals. The total daily dose must not exceed adult dose of 32 mg.

Oral dosing can commence twelve hours later and may be continued for up to 5 days (Table 2).

Table 2: Weight-based dosing for Chemotherapy - Children aged

Weight	Day 1 (a,b)	Days 2-6 (b)
	Up to 3 doses of 0.15mg/kg every 4 hrs	2 mg syrup every 12 hrs
• 10 Kg	Up to 3 doses of 0.15mg/kg every 4 hrs	4 mg syrup or tablet every 12 hrs

a The intravenous dose must not exceed 8mg.

b The total daily dose must not exceed adult dose of 32 mg.

Elderly: Ondansetron hydrochloride is well tolerated by patients over 65 years and no alteration of dosage, dosing frequency or route of administration are required.

Patients with Renal Impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required.

Patients with hepatic Impairment: Clearance of Ondansetron hydrochloride is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8mg should not be exceeded.

Post-operative nausea and vomiting (PONV):

Adults: For the prevention of PONV ondansetron hydrochloride can be administered orally or by intravenous or intramuscular injection.

Ondansetron hydrochloride may be administered as a single dose of 4mg given by intramuscular or slow intravenous injection at induction of anaesthesia.

For treatment of established PONV a single dose of 4mg given by intramuscular or slow intravenous injection is recommended.

Paediatric population

PONV in children aged

For prevention of PONV in paediatric patients having surgery performed under general anaesthesia, a single dose of ondansetron may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg either prior to, at or after induction of anaesthesia.

For the treatment of PONV after surgery in paediatric patients having surgery performed under general anaesthesia, a single dose of ondansetron hydrochloride may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg.

There are no data on the use of ondansetron hydrochloride in the treatment of PONV in children below 2 years of age.

Elderly: There is limited experience in the use of ondansetron hydrochloride in the prevention and treatment of PONV in the elderly, however ondansetron hydrochloride is well tolerated in patients over 65 years receiving chemotherapy.

Patients with renal impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required.

Patients with hepatic impairment: Clearance of ondansetron hydrochloride is significantly reduced and serum half life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8mg should not be exceeded.

Patients with poor sparteine/debrisoquine metabolism: The elimination half-life of ondansetron hydrochloride is not altered in subjects classified as poor metabolisers ofsparteine and debrisoquine. Consequently in such patients repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing are required.

4.3 Contraindications

Hypersensitivity to any component of the preparation.

4.4 Special Warnings And Precautions For Use

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HTs receptor antagonists. Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.

Very rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.

As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.

In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.

This medicinal product contains less than 1mmol (23mg) of sodium in each ampoule. It is essentially 'sodium-free'.

Paediatric Population

Paediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be monitored closely for impaired hepatic function.

CINV

When calculating the dose on an mg/kg basis and administering three doses at 4-hourly intervals, the total daily dose will be higher than if one single dose of 5mg/m² followed by an oral dose is given. The comparative efficacy of these two different dosing regimens has not been investigated in clinical trials. Cross-trial comparison indicates similar efficacy for both regimens (section 5.1).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly co-administered with it. Specific studies have shown that there are no pharmacokinetic interactions when ondansetron is administered with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental or propofol.

Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising ondansetron, enzyme inhibition or reduced activity of one enzyme e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall ondansetron clearance or dose requirement.

Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

Use of ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines) may increase the risk of arrhythmias (see section 4.4).

4.6 Pregnancy And Lactation

Pregnancy

The safety of ondansetron for use in human pregnancy has not been established.

Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo, or foetus, the course of gestation and pre- and post-natal development. However as animal studies are not always predictive of human response the use of ondansetron in pregnancy is not recommended.

Lactation

Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving ondansetron should not breast-feed their babies.

4.7 Effects On Ability To Drive And Use Machines

In psychomotor testing ondansetron does not impair performance nor cause sedation.

4.8 Undesirable Effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (

The following frequencies are estimated at the standard recommended doses of ondansetron according to indication and formulation.

Immune system disorders
Rare:	Immediate hypersensitivity reactions, sometimes severe including anaphylaxis.
Nervous system disorders
Very common:	Headache.
Uncommon:	Seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia), observed without definitive evidence of persistent clinical sequelae.
Rare:	Dizziness during rapid intravenous administration.
Eye disorders
Rare:	Transient visual disturbances (e.g. blurred vision), predominantly during intravenous administration.
Very rare:	Transient blindness, predominantly during intravenous administration. The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic agents, which included cisplatin. Some cases of transient blindness were reported as cortical in origin.
Cardiac disorders
Uncommon:	Arrhythmias, chest pain with or without ST segment depression, bradycardia.
Very rare:	Transient ECG changes including QT interval prolongation, predominantly with intravenous administration of ondansetron.
Vascular disorders
Common:	Sensation of warmth or flushing.
Uncommon:	Hypotension.
Respiratory, thoracic and mediastinal disorders
Uncommon:	Hiccups.
Gastrointestinal disorders
Common:	Constipation.
Hepatobiliary disorders
Uncommon:	Asymptomatic increases in liver function tests. These events were observed commonly in patients receiving chemotherapy with cisplatin.
General disorders and administration site conditions
Common:	Local intravenous injection site reactions (e.g. rash, urticaria, itching), sometimes extending along the drug administration vein.
Paediatric population
The adverse event profiles in children and adolescents were comparable to that seen in adults.

4.9 Overdose

Symptoms and Signs

There is limited experience of ondansetron overdose. In the majority of cases, symptoms were similar to those already reported in patients receiving recommended doses (see section 4.8). Manifestations that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second degree AV block.

Treatment

There is no specific antidote for ondansetron, therefore in all cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate.

The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are unlikely to respond due to the anti-emetic action of ondansetron itself.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code:- A04 Antiemetics and antinauseants

ATC group:- A04AAO 1 Serotonin (5HT₃) antagonist

Ondansetron is a potent, highly selective 5HTs receptor-antagonist. Its precise mode of action in the control of nausea and vomiting is not known. Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine initiating a vomoting reflex by activating vagal afferents via 5HTs receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5HT3 receptors on neurons located both in the peripheral and central nervous system. The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.

Ondansetron does not alter plasma prolactin concentrations. The role of ondansetron in opiate-induced emesis is not yet established.

Paediatric population

CINV

The efficacy of ondansetron in the control of emesis and nausea induced by cancer chemotherapy was assessed in a double-blind randomised trial in 415 patients aged 1 to 18 years (S3AB3006). On the days of chemotherapy, patients received either ondansetron 5 mg/m² intravenous + ondansetron 4 mg orally after 8-12 hrs or ondansetron 0.45 mg/kg intravenous + placebo orally after 8-12 hrs. Post- chemotherapy both groups received 4 mg ondansetron syrup twice daily for 3 days. Complete control of emesis on worst day of chemotherapy was 49% (5 mg/m² intravenous + ondansetron 4 mg orally) and 41% (0.45 mg/kg intravenous + placebo orally). Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 3 days.

A double-blind randomised placebo-controlled trial (S3AB4003) in 438 patients aged 1 to 17 years demonstrated complete control of emesis on worst day of chemotherapy in:

• 73% of patients when ondansetron was administered intravenously at a dose of 5 mg/m² intravenous together with 2-4 mg dexamethasone orally

• 71% of patients when ondansetron was administered as syrup at a dose of 8 mg + 2-4 mg dexamethasone orally on the days of chemotherapy.

Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 2 days.

The efficacy of ondansetron in 75 children aged 6 to 48 months was investigated in an openlabel, non-comparative, single-arm study (S3A40320). All children received three 0.15 mg/kg doses of intravenous ondansetron, administered 30 minutes before the start of chemotherapy and then at four and eight hours after the first dose. Complete control of emesis was achieved in 56% of patients.

Another open-label, non-comparative, single-arm study (S3A239) investigated the efficacy of one intravenous dose of 0.15 mg/kg ondansetron followed by two oral ondansetron doses of 4 mg for children aged < 12 yrs and 8 mg for children aged

PONV

The efficacy of a single dose of ondansetron in the prevention of post-operative nausea and vomiting was investigated in a randomised, double-blind, placebo-controlled study in 670 children aged 1 to 24 months (post-conceptual age

Four double-blind, placebo-controlled studies have been performed in 1469 male and female patients (2 to 12 years of age) undergoing general anaesthesia. Patients were randomised to either single intravenous doses of ondansetron (0.1 mg/kg for paediatric patients weighing 40 kg or less, 4 mg for paediatric patients weighing more than 40 kg; number of patients = 735)) or placebo (number of patients = 734). Study drug was administered over at least 30 seconds, immediately prior to or following anaesthesia induction. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these studies are summarised in Table 3.

Table 3 Prevention and treatment of PONV in Paediatric Patients – Treatment response over 24 hours

Study	Endpoint	Ondansetron %	Placebo	% p value
S3A380	CR	68	39
S3GT09	CR	61	35
S3A381	CR	53	17
S3GT11	no nausea	64	51	0.004
S3GT11	no emesis	60	47	0.004

CR = no emetic episodes, rescue or withdrawal

5.2 Pharmacokinetic Properties

Following oral administration, ondansetron is passively and completely absorbed from the gastrointestinal tract and undergoes first pass metabolism. Peak plasma concentrations of about 30ng/ml are attained approximately 1.5 hours after an 8mg dose. For doses above 8mg the increase in ondansetron systemic exposure with dose is greater than proportional; this may reflect some reduction in first pass metabolism at higher oral doses. Bioavailability, following oral administration, is slightly enhanced by the presence of food but unaffected by antacids. Studies in healthy elderly volunteers have shown slight, but clinically insignificant, age-related increases in both oral bioavailability (65%) and half-life (five hours) of ondansetron. Gender differences were shown in the disposition of ondansetron, with females having a greater rate and extent of absorption following an oral dose and reduced systemic clearance and volume of distribution (adjusted for weight). The disposition of ondansetron following oral, intramuscular (IM) and intravenous (IV) dosing is similar with a terminal half life of about three hours and steady state volume of distribution of about 140L. Equivalent systemic exposure is achieved after IM and IV administration of ondansetron.

A 4mg intravenous infusion of ondansetron given over five minutes results in peak plasma concentrations of about 65ng/ml. Following intramuscular administration of ondansetron, peak plasma concentrations of about 25ng/ml are attained within 10 minutes of injection.

Following administration of ondansetron suppository, plasma ondansetron concentrations become detectable between 15 and 60 minutes after dosing.

Concentrations rise in an essentially linear fashion, until peak concentrations of 20-30ng/ml are attained, typically six hours after dosing. Plasma concentrations then fall, but at a slower rate than observed following oral dosing due to continued absorption of ondansetron. The absolute bioavailability of ondansetron from the suppository is approximately 60% and is not affected by gender. The half life of the elimination phase following suppository administration is determined by the rate of ondansetron absorption, not systemic clearance and is approximately six hours. Females show a small, clinically insignificant, increase in half-life in comparison with males.

Ondansetron is not highly protein bound (70-76%). Ondansetron is cleared from the systemic circulation predominantly by hepatic metabolism through multiple enzymatic pathways. Less than 5% of the absorbed dose is excreted unchanged in the urine. The absence of the enzyme CYP2D6 (the debrisoquine polymorphism) has no effect on ondansetron's pharmacokinetics. The pharmacokinetic properties of ondansetron are unchanged on repeat dosing.

Special Patient Populations

Children and Adolescents (aged 1 month to 17 years)

In paediatric patients aged 1 to 4 months (n=19) undergoing surgery, weight normalised clearance was approximately 30% slower than in patients aged 5 to 24 months (n=22) but comparable to the patients aged 3 to 12 years. The half-life in the patient population aged 1 to 4 month was reported to average 6.7 hours compared to 2.9 hours for patients in the 5 to 24 month and 3 to 12 year age range. The differences in pharmacokinetic parameters in the 1 to 4 month patient population can be explained in part by the higher percentage of total body water in neonates and infants and a higher volume of distribution for water soluble drugs like ondansetron.

In paediatric patients aged 3 to 12 years undergoing elective surgery with general anaesthesia, the absolute values for both the clearance and volume of distribution of ondansetron were reduced in comparison to values with adult patients. Both parameters increased in a linear fashion with weight and by 12 years of age, the values were approaching those of young adults. When clearance and volume of distribution values were normalised by body weight, the values for these parameters were similar between the different age group populations. Use of weight-based dosing compensates for age-related changes and is effective in normalising systemic exposure in paediatric patients.

Population pharmacokinetic analysis was performed on 428 subjects (cancer patients, surgery patients and healthy volunteers) aged 1 month to 44 years following intravenous administration of ondansetron. Based on this analysis, systemic exposure (AUC) of ondansetron following oral or IV dosing in children and adolescents was comparable to adults, with the exception of infants aged 1 to 4 months. Volume was related to age and was lower in adults than in infants and children. Clearance was related to weight but not to age with the exception of infants aged 1 to 4 months. It is difficult to conclude whether there was an additional reduction in clearance related to age in infants 1 to 4 months or simply inherent variability due to the low number of subjects studied in this age group. Since patients less than 6 months of age will only receive a single dose in PONV a decreased clearance is not likely to be clinically relevant.

In patients with renal impairment (creatinine clearance 15-60 ml/min), both systemic clearance and volume of distribution are reduced following IV administration of ondansetron, resulting in a slight, but clinically insignificant, increase in elimination half-life (5.4h). A study in patients with severe renal impairment who required regular haemodialysis (studied between dialyses) showed ondansetron's pharmacokinetics to be essentially unchanged following IV administration.

Specific studies in the elderly or patients with renal impairment have been limited to IV and oral administration. However, it is anticipated that the half-life of ondansetron after rectal administration in these populations will be similar to that seen in healthy volunteers, since the rate of elimination of ondansetron following rectal administration is not determined by systemic clearance.

Following oral, intravenous or intramuscular dosing in patients with severe hepatic impairment, ondansetron's systemic clearance is markedly reduced with prolonged elimination half-lives (15-32 h) and an oral bioavailability approaching 100% due to reduced pre-systemic metabolism. The pharmacokinetics of ondansetron following administration as a suppository have not been evaluated in patients with hepatic impairment.

5.3 Preclinical Safety Data

No additional data of relevance.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Citric acid monhydrate

Sodium citrate

Sodium chloride

Water for injections.

6.2 Incompatibilities

Ondansetron injection should not be administered in the same syringe or infusion as any other medication.

6.3 Shelf Life

36 months (unopened).

After dilution, see section 6.4 Special precautions for storage.

6.4 Special Precautions For Storage

Do not store above 25°C.

Keep the ampoule in the outer carton

Keep out of the reach and sight of children

After dilution:-

Chemical and physical in use stability has been demonstrated for 24 hours at 25°C and 5°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 24 hours at 2-8°C, unless opening and dilution has taken place in controlled and validated aseptic conditions.

6.5 Nature And Contents Of Container

Type I Ph Eur amber glass 3ml capacity ampoules. Each pack contains one, five or ten ampoules.

Type I Ph Eur amber glass 4ml capacity ampoules. Each pack contains one, five or ten ampoules.

6.6 Special Precautions For Disposal And Other Handling

For single use. Discard any unused product immediately after use.

Ondansetron injection should not be autoclaved.

Compatibility with intravenous fluids:

Ondansetron injection should only be admixed with those infusion solutions which are recommended-

Sodium Chloride Intravenous Infusion BP 0.9%w/v

Glucose Intravenous Infusion BP 5%w/v

Mannitol Intravenous Infusion BP 10%w/v

Ringers Intravenous Infusion

Potassium Chloride 0.3%w/v and Sodium Chloride 0.9%w/v Intravenous Infusion BP

Potassium Chloride 0.3%w/v and Glucose 5%w/v Intravenous Infusion BP

In keeping with good pharmaceutical practice dilutions of Ondansetron Injection in intravenous fluids should be prepared at the time of infusion, although chemical and physical in use stability after dilution has been demonstrated for 24 hours at 25°C and 5°C.

Compatibility with other drugs: Ondansetron may be administered by intravenous infusion at 1mg/hour, e.g. from an infusion bag or syringe pump. The following drugs may be administered via the Y-site of the ondansetron giving set for ondansetron concentrations of 16 to 160 micrograms/ml (e.g. 8 mg/500 ml and 8 mg/50 ml respectively):

Cisplatin: Concentrations up to 0.48 mg/ml (e.g. 240 mg in 500 ml) administered over one to eight hours.

5 -Fluorouracil: Concentrations up to 0.8 mg/ml (e.g. 2.4g in 3 litres or 400mg in 500ml) administered at a rate of at least 20ml per hour (500 ml per 24 hours). Higher concentrations of 5-fluorouracil may cause precipitation of ondansetron. The 5-fluorouracil infusion may contain up to 0.045%w/v magnesium chloride in addition to other excipients shown to be compatible.

Carboplatin: Concentrations in the range 0.18mg/ml to 9.9mg/ml (e.g. 90mg in 500ml to 990mg in 100ml), administered over ten minutes to one hour.

Etoposide: Concentrations in the range 0.14 mg/ml to 0.25 mg/ml (e.g. 72mg in 500ml to 250 mg in 1 litre), administered over thirty minutes to one hour.

Ceftazidime: Doses in the range 250 mg to 2000 mg reconstituted with Water for Injections BP as recommended by the manufacturer (e.g. 2.5ml for 250mg and 10ml for 2g ceftazidime) and given as an intravenous bolus injection over approximately five minutes.

Cyclophosphamide: Doses in the range 100mg to 1g, reconstituted with Water for Injections BP, 5ml per 100mg cyclophosphamide, as recommended by the manufacturer and given as an intravenous bolus injection over approximately five minutes.

Doxorubicin: Doses in the range 10-100mg reconstituted with Water for Injections BP, 5ml per 10mg doxorubicin, as recommended by the manufacturer and given as an intravenous bolus injection over approximately five minutes.

Dexamethasone: Dexamethasone sodium phosphate 20mg may be administered as a slow intravenous injection over two to five minutes via the Y-site of an infusion set delivering 8 or 32mg of ondansetron diluted in 50-100ml of a compatible infusion fluid over approximately 15 minutes. Compatibility between dexamethasone sodium phosphate and ondansetron has been demonstrated supporting administration of these drugs through the same giving set resulting in concentrations in line of 32 micrograms to 2.5mg/ml for dexamethasone sodium phosphate and 8 micrograms to 1mg/ml for ondansetron.

7. Marketing Authorisation Holder

Wockhardt UK Ltd

Ash Road North

Wrexham

LL13 9UF

U.K

8. Marketing Authorisation Number(S)

4mg in 2ml ampoule - PL 29831/0154

8mg in 4ml ampoule - PL 29831/0153

9. Date Of First Authorisation/Renewal Of The Authorisation

22^/06/2007

10. Date Of Revision Of The Text

03/09/2010