Wednesday 25 July 2012

Glucophage XR Extended-Release Tablets


Pronunciation: met-FOR-min
Generic Name: Metformin
Brand Name: Examples include Fortomet and Glucophage XR

Glucophage XR Extended-Release Tablets may rarely cause a serious and sometimes fatal condition called lactic acidosis. Most of these cases have occurred in diabetic patients who also have certain kidney problems. The risk of lactic acidosis may be greater if you have liver problems, kidney problems, or heart failure. The risk may also be greater in patients who are elderly or drink alcohol. Lab tests, including kidney function, may be performed while you take Glucophage XR Extended-Release Tablets.


Do not begin to take Glucophage XR Extended-Release Tablets if you are 80 years or older unless lab tests show that you do not have decreased kidney function. Do not take it if you have a severe infection, have low blood oxygen levels, or are dehydrated. Tell your doctor you take Glucophage XR Extended-Release Tablets before you have any surgery or lab procedures.


Contact your doctor right away if you notice symptoms such as fast or difficult breathing; muscle pain or tenderness; slow or irregular heartbeat; unusual drowsiness, dizziness, or light-headedness; unusual stomach discomfort; or unusual weakness or tiredness. Contact your doctor right away if you start to feel unusually cold or if you have a general feeling of being unwell.





Glucophage XR Extended-Release Tablets are used for:

Treating type 2 diabetes. It is used along with diet and exercise. It may be used alone or with other antidiabetic medicines.


Glucophage XR Extended-Release Tablets are a biguanide antidiabetic. It works by decreasing the amount of sugar that the liver produces and the intestines absorb. It also helps to make your body more sensitive to the insulin that you naturally produce.


Do NOT use Glucophage XR Extended-Release Tablets if:


  • you are allergic to any ingredient in Glucophage XR Extended-Release Tablets

  • you have a severe infection, low blood oxygen levels, kidney or liver problems, high blood ketone or acid levels (eg, diabetic ketoacidosis), or dehydration

  • you have had a stroke or a recent heart attack, or you are in shock

  • you are 80 years or older and have not had a kidney function test

  • you will be having surgery or certain lab procedures

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



Before using Glucophage XR Extended-Release Tablets:


Some medical conditions may interact with Glucophage XR Extended-Release Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:


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

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

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

  • if you have heart failure, especially heart failure that is treated by medicine

  • if you have a history of heart problems, lung or breathing problems, thyroid problems, stomach or bowel problems (eg, paralysis, blockage), adrenal or pituitary problems, or lactic acidosis

  • if you have vomiting, diarrhea, poor health or nutrition, low blood calcium or vitamin B12 levels, or anemia, or if you are dehydrated

  • if you have an infection, fever, recent injury, or moderate to severe burns

  • if you drink alcohol or have a history of alcohol abuse

  • if you will be having surgery or certain lab procedures

  • if you are taking a beta-blocker (eg, propranolol)

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


  • Calcium channel blockers (eg, nifedipine), corticosteroids (eg, prednisone), diuretics (eg, furosemide, hydrochlorothiazide), estrogen, hormonal contraceptives (eg, birth control pills), insulin, isoniazid, nicotinic acid, phenothiazine (eg, chlorpromazine), phenytoin, sulfonylureas (eg, glipizide), sympathomimetics (eg, albuterol, pseudoephedrine), or thyroid hormones (eg, levothyroxine) because the risk of high or low blood sugar may be increased

  • Amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin, or medicines that may harm the kidney (eg, aminoglycoside antibiotics [eg, gentamicin], amphotericin B, tacrolimus) because they may increase the risk of Glucophage XR Extended-Release Tablets's side effects. Ask you doctor if you are unsure if any of your medicines might harm the kidney

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


Use Glucophage XR Extended-Release Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.


  • An extra patient leaflet is available with Glucophage XR Extended-Release Tablets. Talk to your pharmacist if you have questions about this information.

  • Take Glucophage XR Extended-Release Tablets by mouth with the evening meal unless your doctor tells you otherwise.

  • Swallow Glucophage XR Extended-Release Tablets whole. Do not break, crush, or chew before swallowing.

  • Take Glucophage XR Extended-Release Tablets on a regular schedule to get the most benefit from it. Taking Glucophage XR Extended-Release Tablets at the same time each day will help you remember to take it.

  • Continue to take Glucophage XR Extended-Release Tablets even if you feel well. Do not miss any doses.

  • If you miss a dose of Glucophage XR Extended-Release Tablets, 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 Glucophage XR Extended-Release Tablets.



Important safety information:


  • Glucophage XR Extended-Release Tablets may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Glucophage XR Extended-Release Tablets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

  • Follow the diet and exercise program given to you by your health care provider.

  • Do not drink large amounts of alcohol while you take Glucophage XR Extended-Release Tablets. Talk to your doctor or health care provider before you drink alcohol while you take Glucophage XR Extended-Release Tablets.

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

  • Be careful not to become dehydrated, especially during hot weather or while you are being active. Dehydration may increase the risk of Glucophage XR Extended-Release Tablets's side effects.

  • If vomiting or diarrhea occurs, you will need to take care not to become dehydrated. Contact your doctor for instructions.

  • You may notice undissolved parts of Glucophage XR Extended-Release Tablets in your stool. This is normal and not a cause for concern.

  • Carry an ID card at all times that says you have diabetes. Check your blood sugar levels as directed by your doctor. If they are often higher or lower than they should be and you take Glucophage XR Extended-Release Tablets exactly as prescribed, tell your doctor.

  • Glucophage XR Extended-Release Tablets does not usually cause low blood sugar. Low blood sugar may be more likely to occur if you skip a meal, exercise heavily, or drink alcohol. It may also be more likely if you take Glucophage XR Extended-Release Tablets along with certain medicines for diabetes (eg, sulfonylureas, insulin). Tell your doctor right away if you experience symptoms of low blood sugar (eg, fast heartbeat, headache, chills, sweating, tremors, increased hunger, vision changes, nervousness, weakness, dizziness, drowsiness, fainting).

  • It is a good idea to carry a reliable source of glucose (eg, tablets or gel) to treat low blood sugar. If this is not available, you should eat or drink a quick source of sugar like table sugar, honey, candy, orange juice, or non-diet soda. This will raise your blood sugar level quickly. Tell your doctor right away if this happens. To prevent low blood sugar, eat meals at the same time each day and do not skip meals.

  • Fever, infection, injury, or surgery may increase your risk of high or low blood sugar levels. If any of these occur, check your blood sugar level closely and tell your doctor right away.

  • Glucophage XR Extended-Release Tablets may commonly cause stomach upset, indigestion, nausea, vomiting, or diarrhea at the beginning of treatment. If you develop unusual or unexpected stomach problems, or if you develop stomach problems later during treatment, contact your doctor at once. This may be a sign of lactic acidosis.

  • Lab tests, including kidney function, fasting blood glucose, hemoglobin A1c, and complete blood cell counts, may be performed while you take Glucophage XR Extended-Release Tablets. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

  • Use Glucophage XR Extended-Release Tablets with caution in the ELDERLY; they may be more sensitive to its effects. Low blood sugar levels may also be more difficult to recognize in the elderly.

  • Glucophage XR Extended-Release Tablets should not be used in CHILDREN younger than 17 years; safety and effectiveness in these children have not been confirmed.

  • PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Glucophage XR Extended-Release Tablets while you are pregnant. It is not known if Glucophage XR Extended-Release Tablets are found in breast milk. Do not breast-feed while taking Glucophage XR Extended-Release Tablets.

When used for long periods of time, Glucophage XR Extended-Release Tablets may not work as well. If your blood sugar has been under control and then becomes hard to manage, contact your doctor. Do not change the dose of your medicine without checking with your doctor.



Possible side effects of Glucophage XR Extended-Release Tablets:


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; gas; headache; indigestion; nausea; stomach pain or upset; temporary metallic taste; vomiting.



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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain or discomfort; dizziness or light-headedness; fast or difficult breathing; feeling of being unusually cold; fever, chills, or persistent sore throat; general feeling of being unwell; muscle pain or weakness; slow or irregular heartbeat; unusual drowsiness; unusual or persistent stomach pain or discomfort; unusual tiredness or weakness.



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: Glucophage XR 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 dizziness or light-headedness; fast or difficult breathing; feeling of being unusually cold; general feeling of being unwell; muscle pain or tenderness; slow or irregular heartbeat; unusual drowsiness; unusual stomach discomfort; unusual weakness or tiredness.


Proper storage of Glucophage XR Extended-Release Tablets:

Store Glucophage XR Extended-Release Tablets at room temperature, between 68 and 77 degrees F (20 and 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 Glucophage XR Extended-Release Tablets out of the reach of children and away from pets.


General information:


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

  • Glucophage XR Extended-Release Tablets 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 Glucophage XR Extended-Release Tablets. 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 Glucophage XR resources


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


Compare Glucophage XR with other medications


  • Diabetes, Type 2
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Tuesday 24 July 2012

Bipolar Disorder Medications


Definition of Bipolar Disorder: Bipolar disorder is characterized by periods of excitability (mania) alternating with periods of depression. The "mood swings" between mania and depression are often very abrupt.

Drugs associated with Bipolar Disorder

The following drugs and medications are in some way related to, or used in the treatment of Bipolar Disorder. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

See sub-topics

Topics under Bipolar Disorder

  • Mania (11 drugs)

  • Severe Mood Dysregulation (3 drugs)

Learn more about Bipolar Disorder





Drug List:

Saturday 21 July 2012

Germoloids Cream





1. Name Of The Medicinal Product



Germoloids Cream


2. Qualitative And Quantitative Composition







Zinc oxide Ph. Eur.

6.6% w/w

Lidocaine hydrochloride Ph. Eur.

0.7% w/w


3. Pharmaceutical Form



Cream for topical and rectal administration.



4. Clinical Particulars



4.1 Therapeutic Indications



The symptomatic relief of pain, swelling, irritation and itching associated with haemorrhoids and pruritus ani.



4.2 Posology And Method Of Administration



Adults and children aged 12 years and over:



Apply at least twice a day with a minimum of three to four hours between applications. Further applications can be made at any time of day and are particularly recommended after bowel movement.



Do not use more than four times in any 24 hour period.



External piles and pruritus ani:



Apply to the affected area.



Internal piles:



Gently insert applicator into the anal opening and expel a small amount of the cream by squeezing the tube gently.



Children under 12 years:



Only as directed by a doctor



The elderly:



Use as per adult directions.



4.3 Contraindications



Hypersensitivity to any of the constituents.



4.4 Special Warnings And Precautions For Use



Persons who continually suffer from haemorrhoids or who have severe haemorrhoids or who experience excessive bleeding, are advised to consult a doctor.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



None known for topical preparations.



4.6 Pregnancy And Lactation



There is a lack of definitive evidence of safety of the product in human pregnancy and lactation. However, lidocaine hydrochloride and zinc oxide have been in wide use for many years without apparent ill consequence. It is not necessary to contraindicate this product in pregnancy and lactation provided caution is exercised and the directions for use are followed. However, as with all medicines, the advice of a doctor should be sought.



4.7 Effects On Ability To Drive And Use Machines



None.



4.8 Undesirable Effects



Very rarely increased irritation may occur at the site of application.



4.9 Overdose



It is very unlikely that overdosage would occur from this pharmaceutical form. Symptoms of lidocaine overdosage would be unlikely to occur even after anal insertion of 25g of cream.



Normally there should be no systemic adverse effects, but at worst CNS and cardiovascular effects are possible. Treatment would be symptomatic after withdrawal of product.



In the case of accidental oral ingestion, the advice of a doctor should be sought.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Zinc oxide has astringent, antiseptic, soothing and protective properties.



Lidocaine hydrochloride has a local anaesthetic action.



The cream base has emollient properties.



5.2 Pharmacokinetic Properties



The product has a local action with minimal risk of systemic effects. Lidocaine has a fast onset and intermediate duration of action. It is partially absorbed but plasma levels will be low in view of the concentration of lidocaine in the product. It undergoes de-ethylation in the liver where clearance approaches the rate of hepatic flow.



5.3 Preclinical Safety Data



Preclinical safety data on these active ingredients in the literature, have not revealed any pertinent and conclusive findings which are of relevance to the recommended dosage and use of the product.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Polawax



White soft paraffin



Methyl salicylate



Methyl hydroxybenzoate (E218)



Butyl hydroxybenzoate



Purified water.



6.2 Incompatibilities



None known.



6.3 Shelf Life



Three years



6.4 Special Precautions For Storage



Do not store above 25oC.



6.5 Nature And Contents Of Container



a) Flexible aluminium tubes internally lacquered, fitted with a polypropylene screw cap. 25, 27.5 or 55g tubes are contained in boxboard cartons, together with a polyethylene screw-on applicator nozzle.



b) Aluminium laminate tube consisting of 150µm Polyethylene /5µm polyacrylate outer layer, 30µm aluminium and an inner layer of 30µm polyacrylate / 60µm polyethylene, fitted with a HD polyethylene shoulder, an aluminium/surlyn tamper evident seal, polypropylene cap and a loose polyethylene screw-on applicator nozzle.



6.6 Special Precautions For Disposal And Other Handling



Not applicable.



Administrative Data


7. Marketing Authorisation Holder



Bayer plc



Trading style: Bayer plc; Consumer Care Division



Bayer House



Strawberry Hill



Newbury



Berkshire



RG14 1JA



United Kingdom



8. Marketing Authorisation Number(S)



PL 00010/0265



9. Date Of First Authorisation/Renewal Of The Authorisation



1st July 2000



10. Date Of Revision Of The Text



February 2006




Carpaquin





Dosage Form: FOR ANIMAL USE ONLY
Carpaquin™ CAPLETS

(carprofen)

ANADA 200-498, Approved by FDA


Non-steroidal anti-inflammatory drug


For oral use in dogs only


CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.



DESCRIPTION:


Carprofen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class that includes ibuprofen, naproxen, and ketoprofen. Carprofen is the nonproprietary designation for a substituted carbazole, 6-chloro-∝-methyl-9H-carbazole-2-acetic acid. The empirical formula is C15H12ClNO2 and the molecular weight 273.72. The chemical structure of carprofen is:



Carprofen is a white, crystalline compound. It is freely soluble in ethanol, but practically insoluble in water at 25°C.



CLINICAL PHARMACOLOGY:


Carprofen is a non-narcotic, non-steroidal anti-inflammatory agent with characteristic analgesic and antipyretic activity approximately equipotent to indomethacin in animal models.1


The mechanism of action of carprofen, like that of other NSAlDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals.2 The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-l is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. The specificity of a particular NSAID for COX-2 versus COX-1 may vary from species to species.3 In an in vitro study using canine cell cultures, carprofen demonstrated selective inhibition of COX-2 versus COX-1.4 Clinical relevance of these data has not been shown. Carprofen has also been shown to inhibit the release of several prostaglandins in two inflammatory cell systems: rat polymorphonuclear leukocytes (PMN) and human rheumatoid synovial cells, indicating inhibition of acute (PMN system) and chronic (synovial cell system) inflammatory reactions.1


Several studies have demonstrated that carprofen has modulatory effects on both humoral and cellular immune responses.5-9 Data also indicate that carprofen inhibits the production of osteoclast-activating factor (OAF), PGE1, and PGE2 by its inhibitory effects on prostaglandin biosynthesis.1


Based upon comparison with data obtained from intravenous administration, carprofen is rapidly and nearly completely absorbed (more than 90% bioavailable) when administered orally.l0 Peak blood plasma concentrations are achieved in 1-3 hours after oral administration of 1, 5, and 25 mg/kg to dogs. The mean terminal half-life of carprofen is approximately 8 hours (range 4.5-9.8 hours) after single oral doses varying from 1-35 mg/kg of body weight. After a 100 mg single intravenous bolus dose, the mean elimination half-life was approximately 11.7 hours in the dog. Carprofen is more than 99% bound to plasma protein and exhibits a very small volume of distribution.


Carprofen is eliminated in the dog primarily by biotransformation in the liver followed by rapid excretion of the resulting metabolites (the ester glucuronide of carprofen and the ether glucuronides of 2 phenolic metabolites, 7-hydroxy-carprofen and 8-hydroxy carprofen) in the feces (70-80%) and urine (10-20%). Some enterohepatic circulation of the drug is observed.



INDICATIONS:


Carprofen is indicated for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.



CONTRAINDICATIONS:


Carprofen should not be used in dogs exhibiting previous hypersensitivity to carprofen.



PRECAUTIONS:


As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal and hepatic toxicity. Effects may result from decreased prostaglandin production and inhibition of the enzyme cyclooxygenase which is responsible for the formation of prostaglandins from arachidonic acid.11-14 When NSAlDs inhibit prostaglandins that cause inflammation they may also inhibit those prostaglandins which maintain normal homeostatic function. These anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease more often than in healthy patients.12,14 NSAID therapy could unmask occult disease which has previously been undiagnosed due to the absence of apparent clinical signs. Patients with underlying renal disease for example, may experience exacerbation or decompensation of their renal disease while on NSAID therapy.11-14 The use of parenteral fluids during surgery should be considered to reduce the potential risk of renal complications when using NSAlDs perioperatively.


Carprofen is an NSAID, and as with others in that class, adverse reactions may occur with its use. The most frequently reported effects have been gastrointestinal signs. Events involving suspected renal, hematologic, neurologic, dermatologic, and hepatic effects have also been reported. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular, and/or hepatic dysfunction. Concurrent administration of potentially nephrotoxic drugs should be approached cautiously, with appropriate monitoring. Since NSAIDs possess the potential to induce gastrointestinal ulcerations and/or gastrointestinal perforations, concomitant use of carprofen and other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided. If additional pain medication is needed after administration of the total daily dose of carprofen, a non-NSAID or non-corticosteroid class of analgesia should be considered. The use of another NSAID is not recommended. Sensitivity to drug-associated adverse reactions varies with the individual patient. Dogs that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Carprofen treatment was not associated with renal toxicity or gastrointestinal ulceration in well-controlled safety studies of up to ten times the dose in dogs.


Carpaquin™ Caplets is not recommended for use in dogs with bleeding disorders (e.g., Von Willebrand's disease), as safety has not been established in dogs with these disorders. The safe use of Carpaquin Caplets in animals less than 6 weeks of age, pregnant dogs, dogs used for breeding purposes, or in lactating bitches has not been established. Studies to determine the activity of carprofen when administered concomitantly with other protein-bound or similarly metabolized drugs have not been conducted.


Drug compatibility should be monitored closely in patients requiring additional therapy. Such drugs commonly used include cardiac, anticonvulsant and behavioral medications. It has been suggested that treatment with carprofen may reduce the level of inhalant anesthetics needed.15


If additional pain medication is warranted after administration of the total daily dose of Carpaquin Caplets, alternative analgesia should be considered. The use of another NSAID is not recommended. Consider appropriate washout times when switching from one NSAID to another or when switching from corticosteroid use to NSAID use.



WARNINGS:


Keep out of reach of children. Not for human use. Consult a physician in cases of accidental ingestion by humans.For use in dogs only. Do not use in cats.


All dogs should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate laboratory tests to establish hematological and serum biochemical baseline data prior to, and periodically during, administration of any NSAID should be considered. Owners should be advised to observe for signs of potential drug toxicity (see Information for Dog Owners, Adverse Reactions, Animal Safety and Post-Approval Experience).



INFORMATION FOR DOG OWNERS:


Carpaquin Caplets, like other drugs of its class, is not free from adverse reactions. Owners should be advised of the potential for adverse reactions and be informed of the clinical signs associated with drug intolerance. Adverse reactions may include decreased appetite, vomiting, diarrhea, dark or tarry stools, increased water consumption, increased urination, pale gums due to anemia, yellowing of gums, skin or white of the eye due to jaundice, lethargy, incoordination, seizure, or behavioral changes.


Serious adverse reactions associated with this drug class can occur without warning and in rare situations result in death (see Adverse Reactions). Owners should be advised to discontinue Carpaquin Caplets therapy and contact their veterinarian immediately if signs of intolerance are observed.


The vast majority of patients with drug related adverse reactions have recovered when the signs are recognized, the drug is withdrawn and veterinary care, if appropriate, is initiated. Owners should be advised of the importance of periodic follow up for all dogs during administration of any NSAID.



ADVERSE REACTIONS:


During investigational studies of osteoarthritis with twice daily administration of 1 mg/lb, no clinically significant adverse reactions were reported. Some clinical signs were observed during field studies (n=297) which were similar for carprofen caplet- and placebo-treated dogs. Incidences of the following were observed in both groups: vomiting (4%), diarrhea (4%), changes in appetite (3%), lethargy (1.4%), behavioral changes (1 %), and constipation (0.3%).The product vehicle served as control.


There were no serious adverse events reported during clinical field studies with once daily oral administration of 2 mg/lb. The following categories of abnormal health observations were reported. The product vehicle served as control.











































Percentage of Dogs with Abnormal Health Observations Reported in Clinical Field Study(2 mg/lb once daily)
Observationcarprofen

(n=129)
Placebo

(n=132)
Inappetence1.61.5
Vomiting3.13.8
Diarrhea/Soft stool3.14.5
Behavior change0.80.8
Dermatitis0.80.8
PU/PD0.8--
SAP increase7.88.3
ALT increase5.44.5
AST increase2.30.8
BUN increase3.11.5
Bilirubinuria16.312.1
Ketonuria14.79.1

Clinical pathology parameters listed represent reports of increases from pre-treatment values; medical judgment is necessary to determine clinical relevance.


During investigational studies of surgical pain for the caplet formulation, no clinically significant adverse reactions were reported. The product vehicle served as control.









































Percentage of Dogs with Abnormal Health Observations Reported in Surgical Pain Field Studies with Caplets (2 mg/lb once daily)

*A single dog may have experienced more than one occurrence of an event.


Observation*carprofen

(n=148)
Placebo

(n=149)
Vomiting10.113.4
Diarrhea/Soft stool6.16.0
Ocular disease2.70
Inappetence1.40
Dermatitis/skin lesion2.01.3
Dysrhythmia0.70
Apnea1.40
Oral/periodontal disease1.40
Pyrexia0.71.3
Urinary tract disease1.41.3
Wound drainage1.40

Post-Approval Experience:


Although not all adverse reactions are reported, the following adverse reactions are based on voluntary post-approval adverse drug experience reporting. The categories of adverse reactions are listed in decreasing order of frequency by body system.


Gastrointestinal: Vomiting, diarrhea, constipation, inappetence, melena, hematemesis, gastrointestinal ulceration, gastrointestinal bleeding, pancreatitis.


Hepatic: Inappetence, vomiting, jaundice, acute hepatic toxicity, hepatic enzyme elevation, abnormal liver function test(s), hyperbilirubinemia, bilirubinuria, hypoalbuminemia. Approximately one-fourth of hepatic reports were in Labrador Retrievers.


Neurologic: Ataxia, paresis, paralysis, seizures, vestibular signs, disorientation.


Urinary: Hematuria, polyuria, polydipsia, urinary incontinence, urinary tract infection, azotemia, acute renal failure, tubular abnormalities including acute tubular necrosis, renal tubular acidosis, glucosuria.


Behavioral: Sedation, lethargy, hyperactivity, restlessness, aggressiveness.


Hematologic:Immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, blood loss anemia, epistaxis.


Dermatologic:Pruritus, increased shedding, alopecia, pyotraumatic moist dermatitis (hot spots), necrotizing panniculitis/vasculitis, ventral ecchymosis.


Immunologic or hypersensitivity:Facial swelling, hives, erythema.


In rare situations, death has been associated with some of the adverse reactions listed above. To report a suspected adverse reaction call 1-877-424-6580.



DOSAGE AND ADMINISTRATION:


Always provide Client Information Sheet with prescription. Carefully consider the potential benefits and risk of Carpaquin and other treatment options before deciding to use Carpaquin. Use the lowest effective dose for the shortest duration consistent with individual response. The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure. Caplets are scored and dosage should be calculated in half-caplet increments.



EFFECTIVENESS:


Confirmation of the effectiveness of carprofen for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain associated with soft tissue and orthopedic surgeries, was demonstrated in 5 placebo-controlled, masked studies examining the anti-inflammatory and analgesic effectiveness of carprofen in various breeds of dogs.


Separate placebo-controlled, masked, multicenter field studies confirmed the anti-inflammatory and analgesic effectiveness of carprofen when dosed at 2 mg/lb once daily or when divided and administered at 1 mg/lb twice daily. In these two field studies, dogs diagnosed with osteoarthritis showed statistically significant overall improvement based on lameness evaluations by the veterinarian and owner observations when administered carprofen at labeled doses.


Separate placebo-controlled, masked, multicenter field studies confirmed the effectiveness of carprofen for the control of postoperative pain when, dosed at 2 mg/lb once daily in various breeds of dogs. In these studies, dogs presented for ovariohysterectomy, cruciate repair and aural surgeries were administered carprofen preoperatively and for a maximum of 3 days (soft tissue) or 4 days (orthopedic) postoperatively. In general, dogs administered carprofen showed statistically significant improvement in pain scores compared to controls.



ANIMAL SAFETY STUDIES:


Laboratory studies in unanesthetized dogs and clinical field studies have demonstrated that carprofen is well tolerated in dogs after oral administration.


In target animal safety studies, carprofen was administered orally to healthy Beagle dogs at 1, 3, and 5 mg/lb twice daily (1, 3 and 5 times the recommended total daily dose) for 42 consecutive days with no significant adverse reactions. Serum albumin for a single female dog receiving 5 mg/lb twice daily decreased to 2.1 g/dL after 2 weeks of treatment, returned to the pre-treatment value (2.6 g/dL) after 4 weeks of treatment, and was 2.3 g/dL at the final 6-week evaluation. Over the 6-week treatment period, black or bloody stools were observed in 1 dog (1 incident) treated with 1 mg/lb twice daily and in 1 dog (2 incidents) treated with 3 mg/lb twice daily. Redness of the colonic mucosa was observed in 1 male that received 3 mg/lb twice daily.


Two of 8 dogs receiving 10 mg/lb orally twice daily (10 times the recommended total daily dose) for 14 days exhibited hypoalbuminemia. The mean albumin level in the dogs receiving this dose was lower (2.38 g/dL) than each of 2 placebo control groups (2.88 and 2.93 g/dL, respectively). Three incidents of black or bloody stool were observed in 1 dog. Five of 8 dogs exhibited reddened areas of duodenal mucosa on gross pathologic examination. Histologic examination of these areas revealed no evidence of ulceration, but did show minimal congestion of the lamina propria in 2 of the 5 dogs.


In separate safety studies lasting 13 and 52 weeks, respectively, dogs were administered orally up to 11.4 mg/lb/day (5.7 times the recommended total daily dose of 2 mg/lb) of carprofen. In both studies, the drug was well tolerated clinically by all of the animals. No gross or histologic changes were seen in any of the treated animals. In both studies, dogs receiving the highest doses had average increases in serum L-alanine aminotransferase (ALT) of approximately 20 IU.


In the 52-week study, minor dermatologic changes occurred in dogs in each of the treatment groups but not in the control dogs. The changes were described as slight redness or rash and were diagnosed as non-specific dermatitis. The possibility exists that these mild lesions were treatment related, but no dose relationship was observed.


Clinical field studies were conducted with 549 dogs of different breeds at the recommended oral doses for 14 days (297 dogs were included in a study evaluating 1 mg/lb twice daily and 252 dogs were included in a separate study evaluating 2 mg/lb once daily). In both studies the drug was clinically well tolerated and the incidence of clinical adverse reactions for carprofen-treated animals was no higher than placebo-treated animals (placebo contained inactive ingredients found in carprofen caplets). For animals receiving 1 mg/lb twice daily, the mean post-treatment serum ALT values were 11 IU greater and 9 IU less than pre-treatment values for dogs receiving carprofen and placebo, respectively. Differences were not statistically significant. For animals receiving 2 mg/lb once daily, the mean post-treatment serum ALT values were 4.5 IU greater and 0.9 IU less than pre-treatment values for dogs receiving carprofen and placebo, respectively. In the latter study, 3 carprofen-treated dogs developed a 3-fold or greater increase in (ALT) and/or (AST) during the course of therapy. One placebo-treated dog had a greater than 2-fold increase in ALT. None of these animals showed clinical signs associated with the laboratory value changes. Changes in clinical laboratory values (hematology and clinical chemistry) were not considered clinically significant. The 1 mg/lb twice daily course of therapy was repeated as needed at 2-week intervals in 244 dogs, some for as long as 5 years.


Clinical field studies were conducted in 297 dogs of different breeds undergoing orthopedic or soft tissue surgery. Dogs were administered 2 mg/lb of carprofen caplets two hours prior to surgery then once daily, as needed for 2 days (soft tissue surgery) or 3 days (orthopedic surgery). Carprofen was well tolerated when used in conjunction with a variety of anesthetic-related drugs. The type and severity of abnormal health observations in carprofen- and placebo-treated animals were approximately equal and few in number (see Adverse Reactions). The most frequent abnormal health observation was vomiting and was observed at approximately the same frequency in carprofen- and placebo-treated animals. Changes in clinicopathologic indices of hematopoetic, renal, hepatic, and clotting function were not clinically significant. The mean post-treatment serum ALT values were 7.3 IU and 2.5 IU less than pre-treatment values for dogs receiving carprofen and placebo, respectively. The mean post-treatment AST values were 3.1 IU less for dogs receiving carprofen and 0.2 IU greater for dogs receiving placebo.



STORAGE:


Store at controlled room temperature 15º-30ºC (59º - 86ºF).



HOW SUPPLIED:


Carpaquin Caplets are scored, and contain 25 mg, 75 mg, or 100 mg of carprofen per caplet. Each caplet size is packaged in bottles containing 36, 72, or 210 caplets.



REFERENCES:


  1. Baruth H, et al: In Anti-Inflammatory and Anti-Rheumatic Drugs, Vol. II, Newer Anti-Inflammatory Drugs, Rainsford KD, ed. CRC Press, Boca Raton, pp. 33-47, 1986.

  2. Vane JR, Botting RM: Mechanism of action of anti-inflammatory drugs. Scand J Rheumatol 25:102, pp. 9-21.

  3. Grossman CJ, Wiseman J, Lucas FS, et al: Inhibition of constitutive and inducible cyclooxygenase activity in human platelets and mononuclear cells by NSAlDs and COX-2 inhibitors. Inflammation Research 44:253-257, 1995.

  4. Ricketts AP, Lundy KM, Seibel SB: Evaluation of selective inhibition of canine cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory drugs. Am J Vet Res 59:11, pp. 1441-1446, November 1998.

  5. Ceuppens JL, et al: Non-steroidal anti-inflammatory agents inhibit the synthesis of IgM rheumatoid factor in vitro. Lancet 1:528, 1982.

  6. Ceuppens JL, et al: Endogenous prostaglandin E2 enhances polyclonal immunoglobulin production by ionically inhibiting T suppressor cell activity. Cell Immunol 70:41, 1982.

  7. Schleimer RP,et al: The effects of prostaglandin synthesis inhibition on the immune response. Immunopharmacology 3:205, 1981.

  8. Leung KH, et al: Modulation of the development of cell mediated immunity: possible roles of the products of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism.Int J Immunopharmacology 4:195, 1982.

  9. Veit BC: Immunoregulatory activity of cultured-induced suppressor macrophages.Cell Immunol 72:14, 1982.

  10. Schmitt M, et al: Biopharmaceutical evaluation of carprofen following single intravenous, oral, and rectal doses in dogs. Biopharm Drug Dispos 11(7):585-94,1990.

  11. Kore AM: Toxicology of nonsteroidal anti-inflammatory drugs. Veterinary Clinics of North America,Small Animal Practice 20, March 1990.

  12. Binns SH: Pathogenesis and pathophysiology of ischemic injury in cases of acute renal failure. Compend for Cont Ed 16:1, January 1994.

  13. Boothe DM: Prostaglandins: Physiology and clinical implications. Compend for Cont Ed 6:11, November 1984.

  14. Rubin SI: Nonsteroidal anti-inflammatory drugs, prostaglandins, and the kidney.JAVMA 188:9, May 1986.

  15. Ko CH, Lange DN, Mandsager RE, et al: Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs. JAVMA 217:1025-1028, 2000.

For a copy of the Material Safety Data Sheet (MSDS) or to report adverse reactions call Nutramax Pharmaceuticals at 1-877-424-6580.


Made in the UK.


Manufactured for:

Nutramax Pharmaceuticals,

a division of Nutramax Laboratories, Inc. Lancaster, SC 29720



NUTRAMAX PharmaceuticalsTM



Dog Owner Information about

Carpaquin™ CAPLETS (carprofen) for Osteoarthritis and Post-Surgical Pain Generic name: carprofen (”car-prô-fen”)


This summary contains important information about Carpaquin™ Caplets. You should read this information before you start giving your dog Carpaquin Caplets and review it each time the prescription is refilled. This sheet is provided only as a summary and does not take the place of instructions from your veterinarian. Talk to your veterinarian if you do not understand any of this information or if you want to know more about Carpaquin Caplets.


What is Carpaquin Caplets?


Carpaquin Caplets is a nonsteroidal anti-inflammatory drug (NSAID) that is used to reduce pain and inflammation (soreness) due to osteoarthritis and pain following surgery in dogs. Carpaquin Caplets is a prescription drug for dogs. It is available as a caplet and is given to dogs by mouth.


Osteoarthritis (OA) is a painful condition caused by "wear and tear" of cartilage and other parts of the joints that may result in the following changes or signs in your dog:


  • Limping or lameness

  • Decreased activity or exercise (reluctance to stand, climb stairs, jump or run, or difficulty in performing these activities)

  • Stiffness or decreased movement of joints

To control surgical pain (e.g. for surgeries such as spays, ear procedures or orthopedic repairs) your veterinarian may administer Carpaquin Caplets before the procedure and recommend that your dog be treated for several days after going home.


What kind of results can I expect when my dog is on Carpaquin Caplets?


While Carpaquin Caplets is not a cure for osteoarthritis, it can relieve the pain and inflammation of OA and improve your dog's mobility.


  • Response varies from dog to dog but can be quite dramatic.

  • In most dogs, improvement can be seen in a matter of days.

  • If Carpaquin Caplets is discontinued or not given as directed, your dog's pain and inflammation may come back.

Who should not take Carpaquin Caplets?


Your dog should not be given Carpaquin Caplets if he/she:


  • Has had an allergic reaction to carprofen, the active ingredient of Carpaquin Caplets.

  • Has had an allergic reaction to aspirin or other NSAIDs (for example deracoxib, etodalac, firocoxib, meloxicam, phenylbutazone or tepoxalin) such as hives, facial swelling, or red or itchy skin.

Carpaquin Caplets should be given to dogs only. Cats should not be given Carpaquin Caplets. Call your veterinarian immediately if your cat receives Carpaquin Caplets. People should not take Carpaquin Caplets. Keep Carpaquin Caplets and all medicines out of reach of children. Call your physician immediately if you accidentally take Carpaquin Caplets.


How to give Carpaquin Caplets to your dog.


Carpaquin Caplets should be given according to your veterinarian's instructions. Your veterinarian will tell you what amount of Carpaquin Caplets is right for your dog and for how long it should be given. Carpaquin Caplets should be given by mouth and may be given with or without food.


What to tell/ask your veterinarian before giving Carpaquin Caplets.


Talk to your veterinarian about:


  • The signs of OA you have observed (for example limping, stiffness).

  • The importance of weight control and exercise in the management of OA.

  • What tests might be done before Carpaquin Caplets is prescribed.

  • How often your dog may need to be examined by your veterinarian.

  • The risks and benefits of using Carpaquin Caplets.

Tell your veterinarian if your dog has ever had the following medical problems:


  • Experienced side effects from Carpaquin Caplets or other NSAIDs, such as aspirin

  • Digestive upset (vomiting and/or diarrhea)

  • Liver disease

  • Kidney disease

  • A bleeding disorder (for example, Von Willebrand's disease)

Tell your veterinarian about:


  • Any other medical problems or allergies that your dog has now or has had.

  • All medicines that you are giving your dog or plan to give your dog, including those you can get without a prescription.

Tell your veterinarian if your dog is:


  • Pregnant, nursing or if you plan to breed your dog.

What are the possible side effects that may occur in my dog during Carpaquin Caplets therapy?


Carpaquin Caplets, like other drugs, may cause some side effects. Serious but rare side effects have been reported in dogs taking NSAIDs, including Carpaquin Caplets. Serious side effects can occur with or without warning and in rare situations result in death.


The most common NSAID-related side effects generally involve the stomach (such as bleeding ulcers), and liver or kidney problems. Look for the following side effects that can indicate your dog may be having a problem with Carpaquin Caplets or may have another medical problem:


  • Decrease or increase in appetite

  • Vomiting

  • Change in bowel movements (such as diarrhea, or black, tarry or bloody stools)

  • Change in behavior (such as decreased or increased activity level, incoordination, seizure or aggression)

  • Yellowing of gums, skin, or whites of the eyes (jaundice)

  • Change in drinking habits (frequency, amount consumed)

  • Change in urination habits (frequency, color, or smell)

  • Change in skin (redness, scabs, or scratching)

It is important to stop therapy and contact your veterinarian immediately if you think your dog has a medical problem or side effect from Carpaquin Caplets therapy. If you have additional questions about possible side effects, talk to your veterinarian.


Can Carpaquin Caplets be given with other medicines?


Carpaquin Caplets should not be given with other NSAIDs (for example aspirin, deracoxib, etodalac, firocoxib, meloxicam, tepoxalin) or steroids (for example cortisone, dexamethasone, prednisone, triamcinolone). Tell your veterinarian about all medicines you have given your dog in the past, and any medicines that you are planning to give with Carpaquin Caplets. This should include other medicines that you can get without a prescription. Your veterinarian may want to check that all of your dog's medicines can be given together.


What do I do in case my dog eats more than the prescribed amount of Carpaquin Caplets?


Contact your veterinarian immediately if your dog eats more than the prescribed amount of Carpaquin Caplets.


What else should I know about Carpaquin Caplets?


This sheet provides a summary of information about Carpaquin Caplets. If you have any questions or concerns about Carpaquin Caplets, or osteoarthritis, or postoperative pain, talk to your veterinarian.


As with all prescribed medicines, Carpaquin Caplets should only be given to the dog for which it was prescribed. It should be given to your dog only for the condition for which it was prescribed.


It is important to periodically discuss your dog's response to Carpaquin Caplets at regular check ups. Your veterinarian will best determine if your dog is responding as expected and if your dog should continue receiving Carpaquin Caplets.


To report a suspected adverse reaction call Nutramax Pharmaceuticals at 1-877-424-6580.


Made in the UK.


Manufactured for:

Nutramax Pharmaceuticals, a division of Nutramax Laboratories, Inc.

Lancaster, SC 29720

001770I01

NUTRAMAX PharmaceuticalsTM



Principal Display Panel – 25 mg Carton


NDC 51904-025-25


CarpaquinTM CAPLETS (carprofen)


25 mg


210 Caplets


FOR ORAL USE IN DOGS ONLY


Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.


Non-steroidal anti-inflammatory drug


ANADA 200-498, Approved by FDA


NUTRAMAX


PharmaceuticalsTM




Principal Display Panel – 25 mg Bottle Label


NDC 51904-025-25


CarpaquinTM CAPLETS (carprofen)


25 mg 210 Caplets


FOR ORAL USE IN DOGS ONLY


Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.


Non-steroidal anti-inflammatory drug


ANADA 200-498, Approved by FDA


NUTRAMAX


PharmaceuticalsTM




Principal Display Panel – 75 mg Carton


NDC 51904-026-25


CarpaquinTM CAPLETS (carprofen)


75 mg


210 Caplets


FOR ORAL USE IN DOGS ONLY


Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.


Non-steroidal anti-inflammatory drug


ANADA 200-498, Approved by FDA


NUTRAMAX


PharmaceuticalsTM




Principal Display Panel – 75 mg Bottle Label


NDC 51904-026-25


CarpaquinTM CAPLETS (carprofen)


75 mg 210 Caplets


FOR ORAL USE IN DOGS ONLY


Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.


Non-steroidal anti-inflammatory drug


ANADA 200-498, Approved by FDA


NUTRAMAX


PharmaceuticalsTM




Principal Display Panel – 100 mg Carton


NDC 51904-027-25


CarpaquinTM CAPLETS (carprofen)


100 mg


210 Caplets


FOR ORAL USE IN DOGS ONLY


Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.


Non-steroidal anti-inflammatory drug


ANADA 200-498, Approved by FDA


NUTRAMAX


PharmaceuticalsTM




Principal Display Panel – 100 mg Bottle Label


NDC 51904-027-25


CarpaquinTM CAPLETS (carprofen)


100 mg 210 Caplets


FOR ORAL USE IN DOGS ONLY


Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.


Non-steroidal anti-inflammatory drug


ANADA 200-498, Approved by FDA


NUTRAMAX


PharmaceuticalsTM










Carpaquin 
carprofen  tablet










Product Information
Product TypePRESCRIPTION ANIMAL DRUGNDC Product Code (Source)51904-025
Route of AdministrationORALDEA Schedule    








Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
carprofen (carprofen)carprofen25 mg





Inactive Ingredients
Ingredient NameStrength
No Inactive Ingredients Found


















Product Characteristics
Colororange (orange)Score2 pieces
ShapeOVAL (OVAL)Size12mm
FlavorImprint Code25;mg;Carpaquin
Contains      






























Packaging
#NDCPackage DescriptionMultilevel Packaging
151904-025-231 BOTTLE In 1 CARTONcontains a BOTTLE
136 TABLET In 1 BOTTLEThis package is contained within the CARTON (51904-025-23)
251904-025-241 BOTTLE In 1 CARTONcontains a BOTTLE
272 TABLET In 1 BOTTLEThis package is contained within the CARTON (51904-025-24)
351904-025-251 BOTTLE In 1 CARTONcontains a BOTTLE
3210 TABLET In 1 BOTTLEThis package is contained within the CARTON (51904-025-25)










Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANADAANADA20049810/11/2010







Carpaquin 
carprofen  tablet










Product Information
Product TypePRESCRIPTION ANIMAL DRUGNDC Product Code (Source)51904-026
Route of AdministrationORALDEA Schedule    








Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
carprofen (carprofen)carprofen75 mg





Inactive Ingredients
Ingredient NameStrength
No Inactive Ingredients Found


















Product Characteristics
Colororange (orange)Score2 pieces
ShapeOVAL (OVAL)Size15mm
FlavorImprint Code75;mg;Carpaquin
Contains      






























Packaging
#NDCPackage DescriptionMultilevel Packaging
151904-026-231 BOTTLE In 1 CARTONcontains a BOTTLE
136 TABLET In 1 BOTTLEThis package is contained within the CARTON (51904-026-23)
251904-026-241 BOTTLE In 1 CARTONcontains a BOTTLE
272 TABLET In 1 BOTTLEThis package is contained within the CARTON (51904-026-24)
351904-026-251 BOTTLE In 1 CARTONcontains a BOTTLE
3210 TABLET In 1 BOTTLEThis package is contained within the CARTON (51904-026-25)










Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANADAANADA20049810/11/2010



Carpaquin 
carprofen  tablet










Product Information
Product TypePRESCRIPTION ANIMAL DRUGNDC Product Code (Source)51904-027
Route of AdministrationORALDEA Schedule    


Active Ingredient/Active Moiety

Tuesday 17 July 2012

NIOPAM 150





1. Name Of The Medicinal Product



NIOPAM 150


2. Qualitative And Quantitative Composition



30.62 w/v Iopamidol equivalent to 150mg iodine/ml.



Each ml contains 306.2 mg Iopamidol.



For excipients, see 6.1.



3. Pharmaceutical Form



Solution for injection.



Clear aqueous solution filled into colourless glass ampoules or bottles.



4. Clinical Particulars



4.1 Therapeutic Indications



X-ray contrast medium for injection, particularly in digital subtraction angiography.



4.2 Posology And Method Of Administration



Route of administration



In digital subtraction angiography:



- Intra-ventricular



- Intra-arterial



Dosage



NIOPAM 150: DOSAGE SCHEDULE










Procedure




Dosage




Intra arterial procedures




Adults : 1-40 ml



Children: 0.5 - 0.75 ml/kg




Ventricular angiography




Children: 1-1.5 ml/kg



Elderly: Dosage as for adults. The lowest effective dose should be used.



Method of administration



No other drugs should be mixed with the contrast medium.



Digital subtraction angiography



For cardiac imaging the contrast medium may be administered intra-arterially by selective catheterisation to provide subtracted images. Niopam 340 and 370 injected intravenously either centrally or peripherally is also recommended for use in this modality.



4.3 Contraindications



Use in patients with proven or suspected hypersensitivity to iodine containing preparations of this type.



4.4 Special Warnings And Precautions For Use



A positive history of allergy, asthma or untoward reaction during previous similar investigations indicates a need for extra caution; the benefit should clearly outweigh the risk in such patients. Appropriate resuscitative measures should be immediately available.



X-ray examination of women should if possible be conducted during the pre-ovulation phase of the menstrual cycle and should be avoided during pregnancy.



When examining small children or babies, do not limit fluid intake before administering a hypertonic contrast solution. Also, correct any existing water and electrolyte imbalance.



Care should be exercised in carrying out radiographic procedures with contrast media in patients with severe functional impairment of the liver or myocardium, severe systemic disease and in myelomatosis (including Waldenströms macroglobulinemia, multiple myeloma).



In the latter condition patients should not be exposed to dehydration; similarly abnormalities of fluid or electrolyte balance should be corrected prior to use.



Particular care should also be exercised in patients with moderate to severe impairment of renal function (as reflected by a raised blood urea) or in diabetes. Substantial deterioration in renal function is minimised if the patient is well hydrated. Renal function parameters should be monitored after the procedure in these patients.



Patients with severe hepato-renal insufficiency should not be examined unless absolutely indicated. Re-examination should be delayed for 5-7 days.



Special care should be exercised when this product is injected into the right heart or pulmonary artery in patients with pulmonary hypertension. Right heart angiography should be carried out only when absolutely indicated.



Niopam should be administered with caution in elderly patients and patients with increased intracranial pressure or suspicion of intracranial tumour, abscess or haematoma, and in those with a history of a previous reaction to contrast media, asthma, allergy, epilepsy, severe cardiovascular disease, renal impairment, chronic alcoholism or multiple sclerosis. Patients with these conditions have an increased risk of neurological complications.



General anaesthesia may be indicated in selected patients. However, a higher incidence of adverse reactions has been reported in these patients, probably due to the hypotensive effect of the anaesthetic.



Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when injected intravenously.



Patients with phaeochromocytoma may develop severe hypertensive crisis following intravascular Iopamidol. Pre-medication with α-receptor blockers is recommended.



The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis.



Patients with congestive heart failure should be observed for several hours following the procedure to detect delayed haemodynamic disturbances, which may be associated with a transitory increase in the circulating osmotic load. All other patients should be observed for at least one hour after the procedure, as most of the adverse events occur in this period. The patient should also be informed that allergic reactions may develop up to several days after the procedure; in such case, a physician should be consulted immediately.



In patients who are known epileptics or have a history of epilepsy, anticonvulsant therapy should be maintained before and following myelographic procedures. In some instances, anticonvulsant therapy may be increased for 48 hours before the examination.



Neuroleptics must be absolutely avoided because they lower the seizure threshold. The same applies to analgesics, anti-emetics, antihistamines and sedatives of the phenothiazine group. Whenever possible, treatment with such drugs should be discontinued at least 48 hours before administration of the contrast medium and not be resumed less than 12 hours after completion of the procedure.



Non-ionic contrast media have less anti-coagulant activity in-vitro than ionic media. Meticulous attention should therefore be paid to angiographic technique. Non-ionic media should not be allowed to remain in contact with blood in the syringe and intravascular catheters should be flushed frequently, to minimise the risk of clotting, which rarely has led to serious thromboembolic complications after procedures.



The presence of renal damage in diabetic patients is one of the factors predisposing to renal impairment following contrast media administration.



This may precipitate lactic acidosis in patients who are taking metformin. As a precaution, metformin should be discontinued at the time of, or prior to, the procedure and withheld for 48 hours subsequent to the procedure and re-instituted only after renal function has been re-evaluated and found to be normal.



Niopam should be used with caution in patients with hyperthyroidism. It is possible that hyperthyroidism may recur in patients previously treated for Graves' disease.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



Thyroid function tests: use of iodinated contrast media may interfere with tests for thyroid function which depend on iodine estimations, such as Protein Binding Iodine and radioactive iodine uptake. As a consequence they will not accurately reflect thyroid function for up to 16 days following administration of iodinated contrast media. Thyroid function tests not depending on iodine estimations, e.g. T3 resin uptake and total or free thyroxine (T4) assays are not affected.



No other specific interference with physiological functions has been noted.



The administration of an X-ray contrast medium in diabetic patients with nephropathy who are taking biguanides may precipitate lactic acidosis.



Arterial thrombosis has been reported when Iopamidol was given following papaverine.



The administration of vasopressors strongly potentiates the neurological effect of the intra-arterial contrast media.



Contrast media may interfere with laboratory tests for bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium, phosphate). These substances should not be assayed during the same day following the administration of contrast media.



4.6 Pregnancy And Lactation



X-ray examination of women should if possible be conducted during the pre-ovulation phase of the menstrual cycle and should be avoided during pregnancy; also, since it has not been demonstrated that Niopam is safe for use in pregnant women, it should be administered only if the procedure is considered essential by the physician.



Niopam is poorly excreted in human milk. From animal experience, Niopam is non toxic in animals after oral administration. Although, no serious adverse reactions have been reported in nursing infants, Niopam should be administered to lactating women only if considered essential by the physician.



4.7 Effects On Ability To Drive And Use Machines



There is no known effect on the ability to drive and operate machines. However, because of the risk of early reactions, driving or operating machinery is not advisable for one hour following the last injection.



4.8 Undesirable Effects



The use of iodinated contrast media may cause untoward side effects. They are usually mild to moderate and transient in nature. However , severe and life threatening reactions sometimes leading to death have been reported.



Anaphylaxis (anaphylactoid reactions/hypersensitivity) may manifest with: mild localized or more diffuse angioneurotic oedema, tongue oedema, laryngospasm or laryngeal oedema, dysphagia, pharyngitis and throat tightness, pharyngolaryngeal pain, cough, conjunctivitis, rhinitis, sneezing, feeling hot, sweating increased, asthenia, dizziness, pallor, dyspnoea, wheezing, bronchospasm, and moderate hypotension. Skin reactions may occur in the form of various types of rash, diffuse erythema, diffuse blisters, urticaria, and pruritus. These reactions, which occur irrespective of the dose administered and the route of administration, may represent the first signs of incipient state of shock. Administration of the contrast medium must be discontinued immediately and – if necessary – specific treatment initiated via a venous access.



More severe reactions involving the cardiovascular system such as vasodilatation with pronounced hypotension, tachycardia, dyspnoea, agitation, cyanosis and loss of consciousness (syncope) may require emergency treatment.



Intravascular administration –Adults



The safety of Iopamidol injection through intravascular administration was evaluated in 2,548 adult patients involved in clinical trials.



The adverse reactions are classified by System Organ Class and frequency, using the following convention: Very common (

























































































System Organ Class




Adverse Reactions


   


Clinical Trials




Post-marketing Surveillance


   


Common



(




Uncommon



(




Rare



(




Frequency unknown


 


Blood and lymphatic system disorders



 

 

 


Thrombocytopenia




Immune system disorders



 

 

 


Anaphylaxis,



Anaphylactoid reaction




Psychiatric disorders



 

 


Confusional state



 


Nervous system disorders




Headache




Dizziness,



Taste alteration




Paraesthesia




Coma,



Transient ischaemic attack,



Syncope,



Depressed level of consciousness or loss of consciousness,



Convulsion,




Eye disorders



 

 

 


Transient blindness,



Visual disturbance,



Conjunctivitis,



Photophobia




Cardiac disorders



 


Cardiac dysrhythmias such as extrasystoles,



atrial fibrillation,



ventricular tachycardia and ventricular fibrillation*




Bradycardia




Myocardial ischaemia or infarction,



Cardiac failure, Cardio-respiratory arrest,



Tachycardia




Vascular disorders



 


Hypotension,



Hypertension,



Flushing



 


Circulatory collapse or shock




Respiratory, thoracic and mediastinal disorders



 

 


Pulmonary oedema,



Asthma,



Bronchospasm




Respiratory arrest,



Respiratory failure,



Acute respiratory distress syndrome,



Respiratory distress,



Apnoea,



Laryngeal oedema,



Dyspnoea




Gastrointestinal disorders




Nausea




Vomiting,



Diarrhea,



Abdominal pain,



Dry mouth



 


Salivary hypersecretion,



Salivary gland enlargement




Skin and subcutaneous tissue disorders



 


Rash,



Urticaria,



Pruritus,



Erythema,



Sweating increased



 


Face oedema,



muco-cutaneous syndromes **




Musculoskeletal and connective tissue disorders



 


Back pain




Muscle spasms




Musculoskeletal pain,



Muscular weakness




Renal and urinary disorders



 


Acute renal failure



 

 


General disorders and administration site conditions




Feeling hot




Chest pain,



Injection site pain***,



Pyrexia,



Feeling cold



 


Rigors,



Pain,



Malaise




Investigations



 


Blood creatinine increased



 


Electrocardiogram change including ST segment depression



* Cardiac reactions may occur as consequences of the coronary catheterization procedural hazard: these complications include coronary artery thrombosis and coronary artery embolism.



** As with other iodinated contrast media, very rare cases of muco-cutaneous syndromes, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome) and erythema multiforme, have been reported following the administration of Iopamidol



*** Injection site pain and swelling may occur. In the majority of cases it is due to extravasation of contrast medium. These reactions are usually transient and result in recovery without sequelae. However, inflammation and even skin necrosis have been seen on very rare occasions. In isolated reports extravasation led to the development of compartment syndrome



Intravascular administration – Pediatric Population



Frequency type and severity of adverse reactions in children are similar to those in adults.



4.9 Overdose



Treatment of overdosage is directed toward the support of all vital functions and the elimination of the contrast medium while maintaining the patient well hydrated.



If needed, haemodialysis can be used to eliminate Iopamidol from the body.



5. Pharmacological Properties



Pharmacotherapeutic group; ATC code: V08A B04



5.1 Pharmacodynamic Properties



Iopamidol is contrast medium belonging to the new generation of non-ionic compound whose solubility is due to the presence of hydrophilic substitutes in the molecule. This results in a solution of low osmolality when compared with ionic media.



Iopamidol has been shown to be effective as an X-ray contrast medium in neuroradiology, angiography, venography, arthrography, urography, cerebral angiography and left ventriculography and coronary arteriography. Its toxicity particularly cardiac and CNS toxicity are less than those of ionic contrast media.



5.2 Pharmacokinetic Properties



The pharmacokinetics of Iopamidol conform to an open two compartment pharmacokinetic model with first order elimination.



Distribution volume is equivalent to extracellular fluid.



Elimination is almost completely through the kidneys. Less that 1% of the administered dose has been recovered in the faeces up to 72 hours after dosing. Elimination is rapid; up to half the administered dose may be recovered in the urine in the first two hours of dosing.



There is no evidence of biotransformation.



Serum protein binding is negligible.



5.3 Preclinical Safety Data



No adverse effects can be predicted from animal toxicology studies other than those documented from human use of Iopamidol.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Excipients are: are trometamol, hydrochloric acid and edetate calcium disodium.



6.2 Incompatibilities



No other drug should be mixed with the contrast medium.



6.3 Shelf Life



5 years.



6.4 Special Precautions For Storage



Protect from light.



6.5 Nature And Contents Of Container



5ml, 10ml and 20ml clear, colourless Type I glass ampoules.



30ml, 50ml, 100ml, 250ml and 200ml clear, colourless Type I or Type II glass bottles with rubber closures and aluminium caps.



6.6 Special Precautions For Disposal And Other Handling



Discard if the solution is not clear of particulate matter.



Exceptionally, the event of crystallisation of Niopam could occur. It has been shown that such a phenomenon is caused by a damaged or defective container and therefore the product should not be used in this case.



The bottle, once opened, must be used immediately.



Any residue of contrast medium must be discarded.



Niopam, as other iodinated contrast media, can react with metallic surfaces containing copper (e.g. brass), therefore the use of equipment, in which the product comes into direct contact with such surfaces, should be avoided.



7. Marketing Authorisation Holder



Bracco U.K. Ltd,



Bracco House, Mercury Park,



Wycombe Lane, Wooburn Green,



Buckinghamshire HP10 OHH



8. Marketing Authorisation Number(S)



PL 18920/0007



9. Date Of First Authorisation/Renewal Of The Authorisation



6th October 1986 / 9th January 2002



10. Date Of Revision Of The Text



15 November 2011