Pediazole

Generic Name: erythromycin and sulfisoxazole (Oral route)

e-rith-roe-MYE-sin eth-il-SUX-i-nate, sul-fi-SOX-a-zole A-se-teel

Commonly used brand name(s)

In the U.S.

• E.S.P.


• Eryzole


• Pediazole

Available Dosage Forms:

• Powder for Suspension

Therapeutic Class: Antibiotic Combination

Chemical Class: Erythromycin

Uses For Pediazole

Erythromycin and sulfisoxazole is a combination antibiotic used to treat ear infections in children. It also may be used for other problems as determined by your doctor. It will not work for colds, flu, or other virus infections.

Erythromycin and sulfisoxazole combination is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not specifically included in product labeling, erythromycin and sulfisoxazole combination is used in certain patients with the following medical condition:

• Sinusitis (sinus infection)

Before Using Pediazole

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

This medicine has been tested in children over the age of 2 months and has not been shown to cause different side effects or problems than it does in adults. This medicine should not be given to infants under 2 months of age unless directed by the child's doctor, because it may cause unwanted effects.

Geriatric

This medicine is intended for use in children and is not generally used in adult patients.

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

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Astemizole


• Bepridil


• Cisapride


• Dihydroergotamine


• Dronedarone


• Ergoloid Mesylates


• Ergonovine


• Ergotamine


• Grepafloxacin


• Levomethadyl


• Mesoridazine


• Methylergonovine


• Methysergide


• Pimozide


• Posaconazole


• Simvastatin


• Sparfloxacin


• Terfenadine


• Thioridazine


• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide


• Ajmaline


• Amiodarone


• Amisulpride


• Amitriptyline


• Amoxapine


• Apomorphine


• Aprindine


• Arsenic Trioxide


• Asenapine


• Atorvastatin


• Azimilide


• Azithromycin


• Bretylium


• Cerivastatin


• Chloral Hydrate


• Chloroquine


• Chlorpromazine


• Ciprofloxacin


• Citalopram


• Clarithromycin


• Clindamycin


• Clomipramine


• Colchicine


• Crizotinib


• Dasatinib


• Desipramine


• Dibenzepin


• Digoxin


• Diltiazem


• Disopyramide


• Dofetilide


• Dolasetron


• Doxepin


• Droperidol


• Encainide


• Enflurane


• Eplerenone


• Everolimus


• Fentanyl


• Flecainide


• Fluconazole


• Fluoxetine


• Foscarnet


• Gatifloxacin


• Gemifloxacin


• Granisetron


• Halofantrine


• Haloperidol


• Halothane


• Hydroquinidine


• Ibutilide


• Iloperidone


• Imipramine


• Isoflurane


• Isradipine


• Itraconazole


• Ketoconazole


• Lapatinib


• Levofloxacin


• Lidoflazine


• Lopinavir


• Lorcainide


• Lovastatin


• Lumefantrine


• Mefloquine


• Methotrexate


• Moxifloxacin


• Nilotinib


• Norfloxacin


• Nortriptyline


• Octreotide


• Ofloxacin


• Ondansetron


• Oxycodone


• Paliperidone


• Pazopanib


• Pentamidine


• Perflutren Lipid Microsphere


• Pirmenol


• Pitavastatin


• Prajmaline


• Probucol


• Procainamide


• Prochlorperazine


• Promethazine


• Propafenone


• Protriptyline


• Quetiapine


• Quinidine


• Quinine


• Ranolazine


• Risperidone


• Saquinavir


• Sematilide


• Sertindole


• Sertraline


• Sodium Phosphate


• Sodium Phosphate, Dibasic


• Sodium Phosphate, Monobasic


• Solifenacin


• Sorafenib


• Sotalol


• Spiramycin


• Sulfamethoxazole


• Sultopride


• Sunitinib


• Tadalafil


• Tedisamil


• Telavancin


• Telithromycin


• Tetrabenazine


• Theophylline


• Tolvaptan


• Toremifene


• Trazodone


• Trifluoperazine


• Trimethoprim


• Trimipramine


• Troleandomycin


• Vandetanib


• Vasopressin


• Vemurafenib


• Verapamil


• Voriconazole


• Warfarin


• Zolmitriptan


• Zotepine

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

• Acetohexamide


• Alfentanil


• Alprazolam


• Anisindione


• Bexarotene


• Budesonide


• Buspirone


• Carbamazepine


• Cilostazol


• Clozapine


• Cyclosporine


• Diazepam


• Dicumarol


• Fesoterodine


• Methylprednisolone


• Midazolam


• Phenprocoumon


• Roflumilast


• Salmeterol


• Sildenafil


• Sirolimus


• Tacrolimus


• Tolterodine


• Triazolam


• Trimetrexate


• Valproic Acid


• Zafirlukast

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Anemia or other blood problems or


• Glucose-6-phosphate dehydrogenase (G6PD) deficiency—Erythromycin and sulfisoxazole may increase the chance of blood problems

• Heart disease—High doses of erythromycin and sulfisoxazole may increase the chance of side effects in patients with a history of an irregular heartbeat

• Kidney disease or


• Liver disease—Patients with liver or kidney disease may have an increased chance of side effects

• Loss of hearing—High doses of erythromycin and sulfisoxazole may increase the chance for hearing loss in some patients

• Porphyria—Erythromycin and sulfisoxazole may increase the chance of a porphyria attack

Proper Use of erythromycin and sulfisoxazole

This section provides information on the proper use of a number of products that contain erythromycin and sulfisoxazole. It may not be specific to Pediazole. Please read with care.

Erythromycin and sulfisoxazole combination is best taken with extra amounts of water and may be taken with food. Additional amounts of water should be taken several times every day, unless otherwise directed by your doctor. Drinking extra water will help to prevent some unwanted effects (e.g., kidney stones) of sulfa medicines.

Do not give this medicine to infants under 2 months of age, unless otherwise directed by your doctor. Sulfa medicines may cause liver problems in these infants.

Use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.

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

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

This medicine works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. Also, it is best to take the doses at evenly spaced times, day and night. For example, if you are to take 4 doses a day, the doses should be spaced about 6 hours apart. If this interferes with your sleep or other daily activities, or if you need help in planning the best times to take your medicine, check with your health care professional.

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 oral dosage form (suspension):
  
  • For infections caused by bacteria:
    
    • Adults and teenagers—This medicine is used only in children.
    
    
    • Children up to 2 months of age—Use is not recommended.
    
    
    • Children 2 months of age and older—Dose is based on body weight:
      
      • For the four-times-a-day dosing schedule
      
      
      • Children weighing less than 8 kilograms (kg) (under 18 pounds): Dose must be determined by your doctor.
      
      
      • Children weighing 8 to 16 kg (18 to 35 pounds): 1/2 teaspoonful (2.5 milliliters [mL]) every six hours for ten days.
      
      
      • Children weighing 16 to 24 kg (35 to 53 pounds): 1 teaspoonful (5 mL) every six hours for ten days.
      
      
      • Children weighing 24 to 32 kg (53 to 70 pounds): 1 1/2 teaspoonfuls (7.5 mL) every six hours for ten days.
      
      
      • Children weighing more than 32 kg (over 70 pounds): 2 teaspoonfuls (10 mL) every six hours for ten days.
      
      
      • For the three-times-a-day dosing schedule
      
      
      • Children weighing less than 6 kg (under 13 pounds): Dose must be determined by your doctor.
      
      
      • Children weighing 6 to 12 kg (13 to 26 pounds): 1/2 teaspoonful (2.5 mL) every eight hours for ten days.
      
      
      • Children weighing 12 to 18 kg (26 to 40 pounds): 1 teaspoonful (5 mL) every eight hours for ten days.
      
      
      • Children weighing 18 to 24 kg (40 to 53 pounds): 1 1/2 teaspoonfuls (7.5 mL) every eight hours for ten days.
      
      
      • Children weighing 24 to 30 kg (53 to 66 pounds): 2 teaspoonfuls (10 mL) every eight hours for ten days.
      
      
      • Children weighing more than 30 kg (over 66 pounds): 2 1/2 teaspoonfuls (12.5 mL) every eight hours for ten days.
      
      
    
    
  
  

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 in the refrigerator. Do not freeze.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Pediazole

It is very important that your doctor check you at regular visits for any blood problems that may be caused by this medicine, especially if you will be taking this medicine for a long time.

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

Erythromycin and sulfisoxazole may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.


• Wear protective clothing, including a hat. Also, wear sunglasses.


• Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your health care professional.


• Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.


• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

Erythromycin and sulfisoxazole combination may cause blood problems. These problems may result in a greater chance of infection, slow healing, and bleeding of the gums. Therefore, you should be careful when using regular toothbrushes, dental floss, and toothpicks. Dental work should be delayed until your blood counts have returned to normal. Check with your medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment.

Pediazole 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

• Itching


• skin rash

Less common

• Aching of joints and muscles


• difficulty in swallowing


• nausea or vomiting


• pale skin


• redness, blistering, peeling, or loosening of skin


• skin rash


• sore throat and fever


• stomach pain, severe


• unusual bleeding or bruising


• unusual tiredness or weakness


• yellow eyes or skin

Rare

• Blood in urine


• dark or amber urine


• irregular or slow heartbeat


• temporary loss of hearing (with kidney disease and high doses)


• lower back pain


• pain or burning while urinating


• pale stools


• recurrent fainting


• severe stomach pain


• swelling of front part of neck

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

More common

• Increased sensitivity to sunlight

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

More common

• Abdominal or stomach cramping and discomfort


• diarrhea


• headache


• loss of appetite


• nausea or vomiting

Less common

• Sore mouth or tongue

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: Pediazole 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 Pediazole resources

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

• Pediazole MedFacts Consumer Leaflet (Wolters Kluwer)


• Pediazole Concise Consumer Information (Cerner Multum)


• Eryzole Concise Consumer Information (Cerner Multum)

Compare Pediazole with other medications

• Otitis Media

Isoptin SR

Generic Name: verapamil (oral) (ver AP a mil)

Brand Names: Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PM

What is verapamil?

Verapamil is in a group of drugs called calcium channel blockers. It works by relaxing the muscles of your heart and blood vessels.

Verapamil is used to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders.

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

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

You should not use verapamil if you are allergic to it, or if you have certain serious heart conditions such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker), low blood pressure, or if you have recently had a heart attack.

Before taking verapamil, tell your doctor if you are allergic to any drugs, or if you have kidney disease, liver disease, congestive heart failure, or a nerve-muscle disorder such as myasthenia gravis or muscular dystrophy.

There are many other drugs that can interact with verapamil. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. Verapamil may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Do not stop taking this medication without first talking to your doctor. If you stop taking verapamil suddenly, your condition may become worse.

Verapamil may be only part of a complete program of treatment that also includes diet, exercise, and other medications. Follow your diet, medication, and exercise routines very closely.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

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

You should not use verapamil if you are allergic to it, or if you have:

• 
  

  certain serious heart conditions, especially "sick sinus syndrome" or "AV block" (unless you have a pacemaker);

  
  


• 
  

  low blood pressure; or

  
  


• 
  

  if you have recently had a heart attack.

  
  

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

• kidney disease;


• liver disease;


• 
  

  congestive heart failure; or

  
  


• 
  

  a nerve-muscle disorder such as myasthenia gravis or muscular dystrophy.

  
  

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

How should I take verapamil?

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

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

Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

If you have trouble swallowing a verapamil capsule whole, ask your doctor or pharmacist if it is safe for you to open the capsule and sprinkle the medicine into a spoonful of applesauce to make swallowing easier. Swallow this mixture right away without chewing. Do not save the mixture for later use. Discard the empty capsule.

Use verapamil regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Do not stop taking this medication without first talking to your doctor. If you stop taking verapamil suddenly, your condition may become worse.

If you are being treated for high blood pressure, keep using this medication even if you feel fine. High blood pressure often has no symptoms.

Verapamil may be only part of a complete program of treatment that also includes diet, exercise, and other medications. Follow your diet, medication, and exercise routines very closely.

Your blood pressure will need to be checked often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using verapamil. You may need to stop using the medicine for a short time. Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

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

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of verapamil can be fatal.

Overdose symptoms may include slow heartbeat and fainting.

What should I avoid while taking verapamil?

Verapamil may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can further lower your blood pressure and may increase certain side effects of verapamil.

Grapefruit and grapefruit juice may interact with verapamil and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Verapamil side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• 
  

  fast or slow heartbeats;

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

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

  
  


• 
  

  restless muscle movements in your eyes, tongue, jaw, or neck;

  
  


• 
  

  feeling short of breath, even with mild exertion;

  
  


• 
  

  swelling, rapid weight gain; or

  
  


• 
  

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

  
  

Less serious side effects may include:

• 
  

  constipation, nausea;

  
  


• 
  

  skin rash or itching;

  
  


• 
  

  dizziness, headache, tired feeling; or

  
  


• 
  

  warmth, itching, redness, or tingly feeling under your skin.

  
  

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 verapamil?

Many drugs can interact with verapamil. Below is just a partial list. Tell your doctor if you are using:

• 
  

  buspirone (BuSpar);

  
  


• 
  

  cimetidine (Tagamet);

  
  


• 
  

  clonidine (Catapres, Clorpres, Kapvay, Nexiclon) or any other blood pressure medications;

  
  


• 
  

  cyclosporine (Gengraf, Neoral, Sandimmune);

  
  


• 
  

  digoxin (digitalis, Lanoxin, Lanoxicaps);

  
  


• 
  

  lithium (Eskalith, LithoBid);

  
  


• 
  

  lovastatin (Mevacor, Advicor) or simvastatin (Zocor, Simcor, Vytorin);

  
  


• 
  

  theophylline (Elixophyllin, Theo-24, Uniphyl);

  
  


• 
  

  an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), rifampin (Rifadin, Rimactane, Rifater), or telithromycin (Ketek);

  
  


• 
  

  an antifungal medication such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend);

  
  


• 
  

  a beta-blocker such as atenolol (Tenormin), bisoprolol (Zebeta, Ziac), metoprolol (Lopressor, Toprol), propranolol (Inderal, InnoPran), sotalol (Betapace), timolol (Blocadren), and others;

  
  


• 
  

  cancer medicine such as cisplatin (Platinol), cyclophosphamide (Cytoxan, Neosar), doxorubicin (Adriamycin), paclitaxel (Taxol), procarbazine (Matulane), vincristine (Oncovin), or vinorelbine (Navelbine);

  
  


• 
  

  cholesterol-lowering drugs such as atorvastatin (Lipitor, Caduet), lovastatin (Mevacor, Altoprev, Advicor), or simvastatin (Zocor, Simcor, Vytorin, Juvisync);

  
  


• 
  

  a heart rhythm medication such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), flecainide (Tambocor), or quinidine (Quin-G);

  
  


• 
  

  HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), or ritonavir (Norvir, Kaletra);

  
  


• 
  

  a sedative such as midazolam (Versed) or triazolam (Halcion); or

  
  


• 
  

  seizure medication such as carbamazepine (Carbatrol, Equetro, Tegretol) or phenobarbital (Solfoton).

  
  

This list is not complete and other drugs may interact with verapamil. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Isoptin SR resources

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

• Isoptin SR Advanced Consumer (Micromedex) - Includes Dosage Information


• Isoptin SR Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Isoptin SR Prescribing Information (FDA)


• Verapamil Prescribing Information (FDA)


• Calan Prescribing Information (FDA)


• Calan MedFacts Consumer Leaflet (Wolters Kluwer)


• Calan SR Prescribing Information (FDA)


• Covera-HS Sustained-Release Tablets (Controlled Onset) MedFacts Consumer Leaflet (Wolters Kluwer)


• Covera-HS Prescribing Information (FDA)


• Verapamil Hydrochloride Monograph (AHFS DI)


• Verelan Prescribing Information (FDA)


• Verelan Sustained-Release Pellet-Filled Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Verelan PM Prescribing Information (FDA)


• Verelan PM Sustained-Release Capsules Controlled Onset MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Isoptin SR with other medications

• Angina
• Arrhythmia
• Bipolar Disorder
• Cluster Headaches
• High Blood Pressure
• Idiopathic Hypertrophic Subaortic Stenosis
• Migraine Prevention
• Nocturnal Leg Cramps
• Supraventricular Tachycardia

Where can I get more information?

• Your pharmacist can provide more information about verapamil.

See also: Isoptin SR side effects (in more detail)

BUFYL 1.25mg / ml and 2microgram / ml Solution for Infusion

1. Name Of The Medicinal Product

BUFYL 1.25mg/ml and 2microgram/ml Solution for Infusion

2. Qualitative And Quantitative Composition

Each 1ml of solution contains 1.25mg bupivacaine hydrochloride and 2 micrograms fentanyl (as fentanyl citrate)

Also contains up to 3.5mg sodium per ml.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Solution for epidural infusion.

Clear, colourless aqueous sterile solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Bufyl solution for infusion is indicated for:

(i) maintaining analgesia post-operatively and

(ii) for maintaining epidural analgesia during labour.

4.2 Posology And Method Of Administration

Route of administration: Epidural Infusion

Bufyl solution for infusion should only be administered epidurally and should only be used by, or under the supervision of, clinicians experienced in regional anaesthesia.

The dose administered must be tailored to the individual patient and procedure. When calculating the dosage for post-operative analgesia, the use of intra-operative bupivacaine and/or fentanyl (or other opioid agonist analgesic) should be taken into account. The rapid injection of bupivacaine with fentanyl solution should be avoided and the maximum accumulated dosage should not exceed 400 mg of bupivacaine and 720 microgram of fentanyl for a 24 hour period in a 70 kg adult.

Note: This formulation is not to be used as a bolus.

Adults:

The length of continuous epidural infusions given post-operatively should be minimized, due to the increased risks of reaching a toxic plasma concentration, inducing local neural injury or local infection. Administration of bupivacaine with fentanyl epidural infusion has not been adequately studied for more than 72 hours. The dosages in the following table are recommended as a guide for use in healthy adults during labour and in the post operative period. It should not be necessary to exceed an infusion dosage of 20mg/hour for bupivacaine. Standard textbooks should be consulted for factors affecting specific block techniques;dosing should be titrated to meet the individual patient requirements and the lowest dose required to provide adequate analgesia should be used.

Bufyl (Bupivacaine 1.25mg/mL + Fentanyl 2 microgram/mL) solution for infusion

Indication	Administration by continuous epidural infusion	Volume mL/hour	Dosage / hour Bupivacaine (mg)	Dosage / hour Fentanyl (microgram)
Analgesia in labour	Lumbar epidural	8 - 15	10 – 18.75	16 - 30
Control of post operative pain	Thoracic, Upper / Lower abdominal epidural	6 - 15	7.5 - 18.75	12 - 30

Careful aspiration before starting the infusion is recommended to prevent intravascular injection. The infusion rate should be slow, with continual assessment of the patient in order to optimise efficacy and safety considerations for the patient and to avoid overdosage.

• Following the start of an infusion a continuous review of the patient is required, including periodic monitoring of the patient's blood pressure/pulse and assessment of pain and sedation at a minimum of 30 minute intervals.

Where conscious, verbal contact with the patient should be maintained throughout.

• Segmental testing of the level of the block is required at least at hourly intervals throughout the time the infusion is administered. Appropriate monitoring should be carried out to detect progressive spread of the block or an increasing density of block.

• Motor block should be assessed periodically using the Bromage score. For obstetric analgesia the test level T5/T6 should be clearly marked, for postoperative analgesia the level of block should be determined relative to the site of surgery.

• Routine maternal cardiovascular and foetal monitoring should be performed. In the case of labour, foetal heart rate should be monitored every 5 minutes for 30 minutes and then as appropriate.

Children:

The use of bupivacaine with fentanyl in children is not recommended since experience in paediatric patients is limited.

Elderly:

Debilitated or elderly patients, including those with advanced liver disease or severe renal dysfunction should be given a reduced dosage commensurate with their physical condition.

Hepatic / Renal Impairment:

Since bupivacaine and fentanyl are metabolized in the liver and excreted via the kidneys, the possibility of medicine accumulation should be considered in patients with hepatic and/or renal impairment, with a possible reduction in dosage depending on the severity of their impairment.

Adequate filtering should be an integral part of the infusion line. The infusion line should be clearly marked to avoid confusion with intravenous lines. Also to avoid confusion, consideration should be given to using a different brand of proprietary pump to that used for IV infusions. In addition, the following pump specifications should be considered:

-accurate infusion rates down to 1ml/hour should be able to be set.

-positive pressure drive, (not gravity feed), should be present.

-a back-up battery should be present.

-an automatic infusion shut-off should be present in case power is lost or the front of the pump is accidentally opened.

4.3 Contraindications

The use of Bufyl solution for infusion is contraindicated in case of:

• allergy or hypersensitivity to bupivacaine, fentanyl or to any of the excipients (See Section 6.1),

• acute respiratory depression,

• acute alcoholism,

• raised intracranial pressure or head injury. As for any narcotic analgesic, fentanyl should not be used in patients with or susceptible to respiratory depression, such as comatose patients who may have head injuries or a brain tumour. Fentanyl may obscure the clinical course of patients with head injury,

• hypovolaemia and complete heart block,

• intravenous regional anaesthesia (Bier's block) as unintentional passage of local anaesthetic into the systemic circulation, despite the use of a tourniquet, may cause systemic toxic reactions,

• obstetrical paracervical block anaesthesia,

• concurrent administration of monoamine oxidase inhibitors (MAOI's) or within 2 weeks of their discontinuation,

Epidural anaesthesia, regardless of the local anaesthetic used, has its own contra-indications which include:

• active disease of the central nervous system such as meningitis, poliomyelitis, intracranial haemorrhage, subacute combined degeneration of the cord due to pernicious anaemia, spina bifida or meningomyelocele and cerebral or spinal tumors,

• tuberculosis of the spine,

• inflammation and/or pyogenic infection of the skin at or adjacent to the site of lumbar puncture,

• a diagnosed arteriovenous malformation in the vertebral column in close proximity to the proposed puncture site,

• cardiogenic shock,

• coagulation disorders or ongoing anticoagulant therapy,

• an expanding cerebral lesion, a tumour, cyst or abscess, which may, if the intracranial pressure is suddenly altered, cause obstruction to the cerebrospinal fluid or blood circulation (the pressure cone).

4.4 Special Warnings And Precautions For Use

Adequate equipment (e.g. oxygen, artificial airways) and medicines (e.g. intravenous fluids, vasopressors) necessary for monitoring and emergency resuscitation should be immediately available. Spinal and epidural anaesthesia may result in sympathetic block with resultant hypotension and bradycardia, therefore an intravenous cannula should be inserted before the local anaesthetic is injected.

Every precaution should be taken to avoid accidental intravascular administration.

The rapid onset of sensory or motor blockade with/without hypotension may indicate accidental intrathecal injection (see Section 4.8)

Caution should be used in patients with hypotension, hypothyroidism, asthma, decreased respiratory reserve, prostatic hypertrophy, convulsive disorders, shock and adrenocortical insufficiency. Local anaesthetics should be given with great caution (if at all) to patients with pre-existing abnormal neurological conditions, e.g. myasthenia gravis.

Debilitated, elderly or young patients may require reduced doses commensurate with their age and physical condition. Since bupivacaine and fentanyl are metabolized in the liver and excreted via the kidneys, the possibility of medicine accumulation should be considered in patients with hepatic and/or renal impairment, with a possible reduction in dosage depending on the severity of their impairment.

Bupivacaine hydrochloride should be administered with caution to patients with cardiovascular disease, hypertension or hyperthyroidism.

This medicine contains approximately 3.5mg sodium per ml. This should be taken into consideration by patients on a controlled sodium (salt) diet.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Anti-arrhythmic medicines

Local anaesthetics of the amide type, such as bupivacaine should be used with caution in patients receiving anti-arrhythmic medicines (e.g. amiodarone) since potentiation of cardiac effects may occur.

Bupivacaine should be used with care in patients receiving anti-arrhythmic drugs with local anaesthetic activity e.g. lignocaine or tocainide, since their toxic effects may be additive.

Profound bradycardia, sinus arrest and hypotension have occurred when patients receiving amiodarone have been given fentanyl for anaesthesia.

CNS depressants

Other CNS depressant agents, e.g. barbiturates, neuroleptics, opioid agonists and general anaesthetics, will have additive or potentiating effects when used with bupivacaine and fentanyl. When patients have received such agents, the dose of bupivacaine with fentanyl required will be less than usual. Likewise, following the administration of bupivacaine with fentanyl, the dose of other CNS depressant agents should be reduced.

The respiratory depressant effect of fentanyl may be enhanced or prolonged by opioid premedication, barbiturates, benzodiazepines, neuroleptics, halogenic gases, alcohol and other non-selective CNS depressants.

Antihypertensives

Antihypertensives like captopril and verapamil may cause severe hypotension and bradycardia in patients given epidural anaesthesia with bupivacaine. Beta-blockers, particularly propranolol, reduce the clearance of bupivacaine and may increase its toxicity.

Neuroleptics

When a neuroleptic such as droperidol is used with fentanyl, pulmonary arterial pressure may be decreased. Hypotension can occur and, possibly hypovolaemia (which should be managed with appropriate parenteral fluids). The following adverse reactions have also been reported: chills, shivering, restlessness, hypertension, postoperative hallucinatory episodes, and transient periods of mental depression. Extrapyramidal symptoms (dystonia, akathisia and oculogyric crisis) have been observed up to 24 hours postoperatively. When they occur, extrapyramidal symptoms can usually be controlled with antiparkinson agents.

Other drug interactions

Concurrent administration of monoamine oxidase inhibitors (MAOI's) or within 2 weeks of their discontinuation, is contraindicsted (see section 4.3)

Epidural anaesthesia is contra-indicated in patients receiving anticoagulant therapy.

Cimetidine may prolong the effects of bupivacaine and fentanyl if used concurrently.

Nitrous oxide has been reported to produce cardiovascular depression when given with high doses of fentanyl.

When fentanyl is used in a single dose, the concomitant use of potent CYP3A4 inhibitors such as ritonavir requires special patient care and observation. With continuous treatment dose reduction of fentanyl may be required to avoid accumulation of fentanyl, which may increase the risk of prolonged or delayed respiratory depression.

4.6 Pregnancy And Lactation

Pregnancy:

Bupivacaine crosses the placenta to a lesser degree than lidocaine or mepivacaine following maternal injection. A lower foetal maternal ratio (0.2-0.4) than for other local anaesthetics (e.g. lignocaine, prilocaine) has been observed for bupivacaine. The greater degree of protein-binding of bupivacaine compared with these other drugs not only limits the amount of bupivacaine available to cross the placenta but also reduces the relative amount of free drug in the foetal circulation.

There is no evidence of untoward effects when used during pregnancy.

Breast-feeding:

With recommended doses, bupivacaine enters breast milk but in such small quantities at therapeutic dose levels that there is generally no risk of affecting the child.

Fentanyl has been shown to have an umbilical cord to maternal vein ratio of 0.06 to 0.44. If fentanyl is administered during childbirth, a narcotic antagonist should be available for use in the unlikely event that respiratory depression occurs in the neonate.

Fentanyl is distributed into human milk in minute quantities and is unlikely to affect a healthy full-term breast feeding infant.

4.7 Effects On Ability To Drive And Use Machines

Even in the case of an early discharge (and clinically tested return of normal motor power) it is not envisaged that a patient should drive or operate machinery within 24 hrs.

4.8 Undesirable Effects

Bupivacaine

Reactions to bupivacaine are similar in character to those observed with other local anaesthetics of the amide type. Adverse reactions may be due to high plasma levels as a result of excessive dosage, rapid absorption, delayed elimination or metabolism, or inadvertent intravascular injection.

Such reactions are systemic in nature and involve the central nervous system and/or the cardiovascular system. Inadvertent subarachnoid injection may lead to cardiovascular collapse, unconsciousness and respiratory arrest. An accidental intrathecal injection may be recognized by early signs of spinal block such as hypotension, bradycardia and difficulty in breathing.

The adverse reactions considered at least possibly related to treatment with Bupivacaine hydrochloride from clinical trials with related products and post-marketing experience are listed below by body system organ class and absolute frequency. Frequencies are defined as very common ( 1/10), common ( 1/100, < 1/10), uncommon ( 1/1,000, < 1/100), rare ( 1/10,000, < 1/1,000) including isolated reports, or not known (identified through post-marketing safety surveillance and the frequency cannot be estimated from the available data).

System Organ Class	Frequency Classification	Adverse Drug Reaction
Immune system disorders	Rare	Allergic reactions, bronchospasm, anaphylactic reaction/ shock (see section 4.4)
Nervous system disorders	Common	Nervousness, paraesthesia, dizziness
	Uncommon	Signs and symptoms of CNS toxicity (euphoria, disorientation, convulsions, circumoral paraesthesia, numbness of the tongue, hyperacusis, visual disturbances, loss of consciousness, tremor, light headedness, tinnitus, pruritis, diaphoresis, dysarthria, muscle twitching)
	Rare	Weakness, persistent anaesthesia, loss of sphincter control, neuropathy, peripheral nerve injury, arachnoiditis, paresis and paraplegia
Eye disorders	Rare	Diplopia, miosis
Cardiac disorders	Common	Bradycardia (see section 4.4)
	Rare	Cardiovascular collapse or cardiac arrest (see section 4.4), cardiac arrhythmias
Vascular disorders	Very Common	Hypotension (see section 4.4)
	Common	Hypertension (see section 4.5)
Respiratory disorders	Rare	Laryngospasm, respiratory depression or respiratory arrest
Gastrointestinal disorders	Very Common	Nausea
	Common	Vomiting
Renal and Urinary	Common	Urinary retention

Fentanyl

The following table displays ADRs that have been reported with the use of fentanyl IV from either clinical trials or post-marketing experiences.

System Organ Class	Adverse Drug Reactions
Frequency Category
Very Common	Common	Uncommon	Not Known
Immune System Disorders				Hypersensitivity (such as anaphylactic shock, anaphylactic reaction, urticaria)
Psychiatric Disorders		Agitation	Changes in mood, hallucinations
Nervous System Disorders	Muscle rigidity (which may also involve the thoracic muscles)	Dyskinesia; sedation; dizziness, drowsiness, confusion	Headache, facial flushing, vertigo, restlessness	Convulsions; loss of consciousness; myoclonus; dyskinesia, raised intracranial pressure
Eye Disorders		Visual disturbance	Miosis
Cardiac Disorders		Bradycardia; Tachycardia; Arrhythmia	Palpitations	Cardiac arrest
Vascular Disorders		Hypotension; Hypertension; Venous pain	Phlebitis; blood pressure fluctuation; orthostatic hypotension
Respiratory, Thoracic and Mediastinal Disorders		Laryngospasm; Bronchospasm; Apnoea	Hyperventilation; Hiccups	Respiratory depression
Gastrointestinal Disorders	Nausea; Vomiting		Dry mouth, constipation
Skin and Subcutaneous Tissue Disorders		Allergic dermatitis		Pruritus
General Disorders and Administration Site Conditions			Chills, hypothermia, sweating, micturition difficulties
Injury, Poisoning and Procedural Complications		Postoperative confusion	Airway complication of anaesthesia

4.9 Overdose

With accidental intravascular injections, the acute toxic systemic effect of bupivacaine will be obvious within 1-3 minutes, while with overdosage, peak plasma concentrations may not be reached for 20-30 minutes depending on the site of injection with signs of toxicity thus being delayed. Toxic reactions originate mainly in the central nervous and the cardiovascular systems. Pronounced acidosis, hyperkalaemia or hypoxia in the patient may increase the risk and severity of toxic reactions.

Central nervous system

Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors are more serious and precede the onset of generalized convulsions. These signs must not be mistaken for a neurotic behaviour. Unconsciousness and grand mal convulsions may follow which may last from a few seconds to several minutes. Hypoxia and hypercarbia can occur rapidly following convulsions due to the increased muscular activity, together with the interference with normal respiration and loss of airway patency. In severe cases apnoea may occur.

Recovery due to redistribution of the local anaesthetic medicine from the central nervous system and metabolism may be rapid unless large amounts of the medicine have been injected.

During epidural analgesia, a marked fall in blood pressure and/or intercostal paralysis may be seen, possibly due to the use of excessive doses or due to improper positioning of the patient (e.g. women in labour).

Cardiovascular system

Effects on the cardiovascular system may be seen in severe cases. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations.

Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with medicines such as a benzodiazepine or barbiturate.

Respiratory system

Overdosage due to fentanyl may result in narcosis, cardiorespiratory depression accompanied by cyanosis, followed by a fall in body temperature, circulatory collapse, coma and possibly death.

High doses of fentanyl may produce motor stimulation and muscle rigidity, particularly involving the muscles of respiration. Muscular rigidity may be associated with reduced pulmonary compliance and/or apnoea, laryngospasm or bronchospasm. This effect is related to the dose and speed of injection and may be reduced by slow infusion. It is unlikely to arise when recommended doses are used in epidural infusion.

Treatment of Overdosage

If signs of acute systemic toxicity appear, infusion of the local anaesthetic should be stopped immediately. If convulsions occur they should be treated immediately. The objectives of treatment are to maintain oxygenation, stop the convulsions and support the circulation. Oxygen must be given and ventilation assisted if necessary (mask and bag). An anticonvulsant should be given IV if the convulsions do not stop spontaneously in 15-20 seconds. Thiopentone 75-125 mg by slow intravenous injection will abort the convulsions rapidly. Alternatively intravenous diazepam 5-10 mg may be used, although its action is slower.

Mangement of respiratory depression

If respiratory depression occurs, assisted respiration and, if necessary, intravenous administration of a single dose of a neuromuscular blocking agent compatible with the patient's condition, such as suxamethonium will provide adequate ventilation without reversing analgesia. Suxamethonium which will stop the muscle convulsions rapidly, will require tracheal intubation and controlled ventilation and should only be used by those familiar with these procedures.

A specific narcotic antagonist, such as nalorphine or naloxone, should be available for use as indicated to manage respiratory depression. This does not preclude the use of more immediate countermeasures. Though opioid antagonists (e.g. naloxone) can immediately reverse the respiratory depression they will also reverse the central analgesic effect due to fentanyl, although the epidural analgesia may not be altered. The duration of respiratory depression following overdosage of fentanyl is usually longer than the duration of narcotic antagonist action.

Management of cardiovascular depression

Should circulatory arrest occur, immediate cardiopulmonary resuscitation should be instituted. In the presence of hypoventilation or apnoea, oxygen should be administered and respiration assisted or controlled as necessary. A patent airway must be maintained. Optimal oxygenation and ventilation and circulatory support, as well as treatment of acidosis, are of vital importance since hypoxia and acidosis will increase the systemic toxicity of local anaesthetics. Bradycardia and other cholinergic effects can be controlled with the appropriate dose of atropine. The inclusion of atropine or other anticholinergic agents in the pre-anaesthetic regimen tends to reduce the occurrence of such effects. If cardiovascular depression is evident (hypotension, bradycardia), a pressor drug like ephedrine 3-6 mg should be given by slow intravenous injection and repeated, if necessary, every 3-4 minutes according to response to a maximum of 30mg. Posture improvement with elevation of the legs, left lateral displacement (if pregnant) and prophylactic volume loading with intravenous fluids should be initiated as appropriate.

The patient should be carefully observed for 24 hours; body warmth and adequate fluid intake should be maintained. If severe or persistent hypotension occurs, the possibility of hypovolaemia should be considered and managed with appropriate parenteral fluid therapy.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group (ATC code): N01B B51

Bupivacaine

Bupivacaine Hydrochloride is a long acting local anaesthetic of the amide type. It prevents the generation and conduction of the nerve impulse by decreasing the permeability of the nerve cell membrane to sodium ions. As well as blocking conduction in nerve axons in the peripheral nervous system, local anaesthetics interfere with the function of all organs in which conduction or transmission of impulses occur.

Systemic absorption of local anaesthetics produces effects on the cardiovascular and central nervous systems (CNS). At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias, and cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Recent clinical reports and animal research suggest that these cardiovascular changes are more likely to occur after unintended direct intravascular injection of bupivacaine. Therefore, when epidural anaesthesia with bupivacaine is considered, incremental dosing is necessary.

Fentanyl

Fentanyl citrate a potent narcotic analgesic is a synthetic opiate with a clinical potency of 50 to 100 times that of morphine. Its onset of action is rapid and its duration of action is short. In man, a single IV dose of 0.5-1 mg/70 kg body weight immediately produces a pronounced state of surgical analgesia, respiratory depression, bradycardia and other typical morphine-like effects. The duration of action of the peak effects is about 30 minutes. The principal actions of therapeutic value are analgesia and sedation. When used with a neuroleptic agent it can induce a state of neuroleptanalgesia. As with other narcotic analgesics, the effect of fentanyl on respiratory depression increases as the drug dosage is increased. All potent morphine-like drugs produce relief from pain, ventilatory depression, emesis, constipation, physical dependence, certain vagal effects and varying degrees of sedation. Fentanyl, however, differs from morphine not only by its short duration of action but also by its lack of emetic effect and minimal hypotensive activity in animals. Epidural fentanyl enhances the epidural analgesia achieved with bupivacaine.

5.2 Pharmacokinetic Properties

Bupivacaine

Absorption & Distribution

Bupivacaine is a long acting, amide type local anaesthetic chemically related to lignocaine and mepivacaine. It is approximately four times as potent as lignocaine. Bupivacaine has a pKa of 8.1 and is extensively bound to plasma proteins. Bupivacaine exhibits a high degree of lipid solubility with an oil/water partition coefficient of 27.5. These factors contribute to its prolonged duration of action.

The onset of blockade is slower than with lignocaine, especially when anaesthetizing large nerves. When used in low concentrations (2.5 mg/mL or less) there is less effect on motor nerve fibres and the duration of action is shorter. Low concentrations may, however, be used with advantage for prolonged pain relief, e.g. in labour or postoperatively.

After epidural injection peak plasma levels of bupivacaine in the blood are reached within 30 to 45 minutes, followed by a decline to insignificant levels during the next 3 to 6 hours. Intercostal blocks give the highest peak plasma concentration due to a rapid absorption (maximum plasma concentrations in the order of 1-4 mg/L after a 400 mg dose), while epidural and major plexus blocks result in intermediate plasma concentrations.. In children rapid absorption and high plasma concentrations (in the order of 1-1.5 mg/L after a dose of 3 mg/kg) are seen with caudal block.

Absorption of bupivacaine from the epidural space occurs in 2 phases; the first phase is in the order of 7 minutes and the second is in 6 hours. The slow absorption is rate-limiting in the elimination of bupivacaine, which explains why the apparent elimination half-life after epidural administration is longer than after intravenous administration.

Metabolism & Excretion

Bupivacaine is excreted in the urine principally as metabolites with about 6% as unchanged medicine. Following epidural administration the urinary recovery of unchanged bupivacaine is about 0.2%, of pipecolylxylidine (PPX) about 1% and of 4-hydroxy-bupivacaine about 0.1% of the administered dose.

Various pharmacokinetic parameters can be significantly altered by a number of factors including the presence of hepatic and renal disease, route of administration, age of the patient and certain concomitant medication. The drug crosses the placenta.

Fentanyl

Absorption & Distribution

Fentanyl is a lipid-soluble drug and its pharmacokinetics can be described in terms of a three-compartment model. Following intravenous injection, there is a short distribution phase during which high concentrations of fentanyl are achieved quickly in well-perfused tissues such as the lungs, kidneys and brain.

Metabolism & Excretion

The drug is redistributed to other tissues; it accumulates more slowly in skeletal muscle and yet more slowly in fat, from which it is gradually released into the blood. Up to 80% of fentanyl is bound to plasma proteins. Fentanyl is primarily metabolized in the liver, probably by N-dealkylation, and it is excreted mainly in the urine with less than 10% representing the unchanged drug. The drug clearance in ml/min/kg is 13±2 with a volume of distribution in litres/kg of 4.0±0.4. Estimates of terminal half-life of fentanyl range from 141 to 853 minutes with an average of 3.7 hours.

5.3 Preclinical Safety Data

No further relevant information other than that which is included in other sections of the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium chloride, Sodium hydroxide (for pH adjustment), Water for injections.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. The pH range is 5.0 to 6.5.

6.3 Shelf Life

3 years

After opening, the product should be used immediately. The product is for single use only and should not be used for more than 24 hours.

6.4 Special Precautions For Storage

Not applicable.

6.5 Nature And Contents Of Container

250ml or 500ml polypropylene infusion bags.

6.6 Special Precautions For Disposal And Other Handling

Solutions showing discolouration and unused portions of solutions should be discarded. For single use only. Do not reconnect partially used bags.

7. Marketing Authorisation Holder

Antigen International Limited

Roscrea,

Co. Tipperary,

Ireland

8. Marketing Authorisation Number(S)

PL 02848/0237

9. Date Of First Authorisation/Renewal Of The Authorisation

14/09/2011

10. Date Of Revision Of The Text

14/09/2011

Tramadol Extended-Release Capsules

Pronunciation: TRAM-a-dol
Generic Name: Tramadol
Brand Name: ConZip

Tramadol Extended-Release Capsules are used for:

Treating moderate to moderately severe chronic pain in certain patients.

Tramadol Extended-Release Capsules are an analgesic. It works in certain areas of the brain and nervous system to decrease pain.

Do NOT use Tramadol Extended-Release Capsules if:

• you are allergic to any ingredient in Tramadol Extended-Release Capsules


• you have had a severe allergic reaction (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue) to codeine or another opioid (eg, morphine)


• you have suicidal thoughts or actions or a history of alcohol or other substance abuse or addiction


• you are intoxicated with alcohol, opioids or narcotics (eg, codeine, morphine), or sedatives or sleeping medicines (eg, temazepam, zolpidem)


• you have severe liver or kidney problems


• you are taking carbamazepine, nefazodone, sodium oxybate (GHB), a thioxanthene (eg, thiothixene), or another product that contains tramadol

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

Before using Tramadol Extended-Release Capsules:

Some medical conditions may interact with Tramadol Extended-Release Capsules. 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 (especially depression medicines) or nonprescription medicine, herbal preparation, or dietary supplement


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


• if you have bladder blockage; are at risk for seizures; or have a history of liver, kidney, or thyroid problems; seizures (eg, epilepsy); heart problems (eg, cor pulmonale); pancreas problems; prostate problems; or metabolism problems


• you have severe or persistent diarrhea due to taking an antibiotic


• if you have or recently have had any head injury, brain injury or tumor, increased pressure in the brain, or infection of the brain or nervous system


• if you have a history of recent stomach or bowel surgery, or any other stomach or bowel problems (eg, pain, inflammation, ulcers)


• if you have slow or shallow breathing, high levels of carbon dioxide in the blood (hypercapnia), or you have a history of lung or breathing problems (eg, asthma, chronic obstructive pulmonary disease [COPD])


• if you drink alcohol; you are going through withdrawal from alcohol or other substances; or you have a history of alcohol or other substance abuse or addiction, mood or mental problems (eg, depression), or suicidal thoughts or actions

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

• Alpha-2 receptor blockers (eg, yohimbine), azole antifungals (eg, ketoconazole), linezolid, lithium, macrolide antibiotics (eg, erythromycin), monoamine oxidase inhibitors (MAOIs) (eg, phenelzine, selegiline), nefazodone, quinidine, selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, paroxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine), St. John's wort, tricyclic antidepressants (eg, amitriptyline), or "triptans" (eg, sumatriptan) because serotonin syndrome may occur


• Anorexiants (eg, phentermine), butyrophenones (eg, haloperidol), cyclobenzaprine, furazolidone, loxapine, certain medicines for mental or mood disorders (eg, olanzapine), molindone, opioid pain medicines (eg, codeine, hydrocodone), phenothiazines (eg, promethazine), sleeping medicines (eg, zolpidem), sodium oxybate (GHB), thioxanthenes (eg, thiothixene), or tiagabine because the risk of side effects, including excessive drowsiness, trouble breathing, liver problems, or seizures, may be increased


• Carbamazepine because it may decrease Tramadol Extended-Release Capsules's effectiveness; the risk of seizures may also be increased


• Other products containing tramadol because they may increase the risk of Tramadol Extended-Release Capsules's side effects


• Rifampin because it may decrease Tramadol Extended-Release Capsules's effectiveness


• Anticoagulants (eg, warfarin) or digoxin because the risk of their side effects may be increased by Tramadol Extended-Release Capsules

This may not be a complete list of all interactions that may occur. Ask your health care provider if Tramadol Extended-Release Capsules 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 Tramadol Extended-Release Capsules:

Use Tramadol Extended-Release Capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Tramadol Extended-Release Capsules by mouth with or without food.


• Swallow Tramadol Extended-Release Capsules whole with liquid. Do not break, crush, dissolve, or chew before swallowing.


• Take Tramadol Extended-Release Capsules at the same time each day.


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

Ask your health care provider any questions you may have about how to use Tramadol Extended-Release Capsules.

Important safety information:

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


• Do not drink alcohol while you are taking Tramadol Extended-Release Capsules.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers, narcotic pain medicines) while you are using Tramadol Extended-Release Capsules; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Tramadol Extended-Release Capsules may cause dizziness; alcohol, hot weather, exercise, or fever may increase this effect. To prevent it, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of this effect.


• Do NOT take more than the recommended dose or take for longer than prescribed without checking with your doctor.


• Tell your doctor or dentist that you take Tramadol Extended-Release Capsules before you receive any medical or dental care, emergency care, or surgery.


• Tramadol Extended-Release Capsules may increase your risk of seizures. Your risk may be greater if you also have certain medical conditions, use certain medicines, or if you use a lot of alcohol. Talk to your doctor to see if you may have a greater risk of seizures while taking Tramadol Extended-Release Capsules.


• Serotonin syndrome is a possibly fatal syndrome that can be caused by Tramadol Extended-Release Capsules. Your risk may be greater if you take Tramadol Extended-Release Capsules with certain other medicines (eg, "triptans," MAOIs, antidepressants). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.


• Use Tramadol Extended-Release Capsules with caution in the ELDERLY; they may be more sensitive to its effects, especially constipation, weakness or tiredness, dizziness, drowsiness, severe light-headedness, nausea, or indigestion.


• Tramadol Extended-Release Capsules should not be used in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Tramadol Extended-Release Capsules has been shown to cause harm to the fetus. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Tramadol Extended-Release Capsules while you are pregnant. Tramadol Extended-Release Capsules are found in breast milk. Do not breast-feed while taking Tramadol Extended-Release Capsules.

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

Some people who use Tramadol Extended-Release Capsules for a long time without a break may develop a physical need to continue taking it. This is known as physical DEPENDENCE.

Do not suddenly stop taking Tramadol Extended-Release Capsules. If you suddenly stop it, you may experience WITHDRAWAL symptoms, including anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping. If you need to stop Tramadol Extended-Release Capsules, your doctor will lower your dose over time.

Possible side effects of Tramadol Extended-Release Capsules:

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

Constipation; dizziness; drowsiness; dry mouth; headache; increased sweating; loss of appetite; mild itching; nausea; trouble sleeping; vomiting; weakness.

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); burning, numbness, or tingling; chest pain; confusion; difficult or painful urination; disorientation; excessive sweating; fainting; fast or irregular heartbeat; fever; hallucinations; loss of coordination; mood or mental changes (eg, depression, agitation); red, blistered, swollen, or peeling skin; seizures; severe dizziness or light-headedness; severe nausea, vomiting, or diarrhea; severe or persistent headache; slow or shallow breathing; suicidal thoughts or behaviors; tremor; vision problems; wheezing.

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: Tramadol side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include bluish skin; cold, clammy skin; difficult, shallow, or slow breathing; drowsiness leading to unresponsiveness or coma; excessive sweating; fainting; limp muscles; pinpoint pupils; seizures; severe or persistent dizziness or light-headedness; slow or irregular heartbeat.

Proper storage of Tramadol Extended-Release Capsules:

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

General information:

• If you have any questions about Tramadol Extended-Release Capsules, please talk with your doctor, pharmacist, or other health care provider.


• Tramadol Extended-Release Capsules are 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 Tramadol Extended-Release Capsules. 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.

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