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)

Observation	carprofen (n=129)	Placebo (n=132)
Inappetence	1.6	1.5
Vomiting	3.1	3.8
Diarrhea/Soft stool	3.1	4.5
Behavior change	0.8	0.8
Dermatitis	0.8	0.8
PU/PD	0.8	--
SAP increase	7.8	8.3
ALT increase	5.4	4.5
AST increase	2.3	0.8
BUN increase	3.1	1.5
Bilirubinuria	16.3	12.1
Ketonuria	14.7	9.1

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)
Vomiting	10.1	13.4
Diarrhea/Soft stool	6.1	6.0
Ocular disease	2.7	0
Inappetence	1.4	0
Dermatitis/skin lesion	2.0	1.3
Dysrhythmia	0.7	0
Apnea	1.4	0
Oral/periodontal disease	1.4	0
Pyrexia	0.7	1.3
Urinary tract disease	1.4	1.3
Wound drainage	1.4	0

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 Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51904-025 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength carprofen (carprofen) carprofen 25 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color orange (orange) Score 2 pieces Shape OVAL (OVAL) Size 12mm Flavor Imprint Code 25;mg;Carpaquin Contains

Packaging # NDC Package Description Multilevel Packaging 1 51904-025-23 1 BOTTLE In 1 CARTON contains a BOTTLE 1 36 TABLET In 1 BOTTLE This package is contained within the CARTON (51904-025-23) 2 51904-025-24 1 BOTTLE In 1 CARTON contains a BOTTLE 2 72 TABLET In 1 BOTTLE This package is contained within the CARTON (51904-025-24) 3 51904-025-25 1 BOTTLE In 1 CARTON contains a BOTTLE 3 210 TABLET In 1 BOTTLE This package is contained within the CARTON (51904-025-25)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANADA	ANADA200498	10/11/2010

Carpaquin  carprofen  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51904-026 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength carprofen (carprofen) carprofen 75 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color orange (orange) Score 2 pieces Shape OVAL (OVAL) Size 15mm Flavor Imprint Code 75;mg;Carpaquin Contains

Packaging # NDC Package Description Multilevel Packaging 1 51904-026-23 1 BOTTLE In 1 CARTON contains a BOTTLE 1 36 TABLET In 1 BOTTLE This package is contained within the CARTON (51904-026-23) 2 51904-026-24 1 BOTTLE In 1 CARTON contains a BOTTLE 2 72 TABLET In 1 BOTTLE This package is contained within the CARTON (51904-026-24) 3 51904-026-25 1 BOTTLE In 1 CARTON contains a BOTTLE 3 210 TABLET In 1 BOTTLE This package is contained within the CARTON (51904-026-25)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANADA	ANADA200498	10/11/2010

Carpaquin  carprofen  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51904-027 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety

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

6^th October 1986 / 9^th January 2002

10. Date Of Revision Of The Text

15 November 2011

Covonia Night Time Formula

1. Name Of The Medicinal Product

Covonia Night Time Formula.

2. Qualitative And Quantitative Composition

Dextromethorphan Hydrobromide Ph.Eur.	6.65mg/5ml dose.
Diphenhydramine Hydrochloride Ph.Eur.	10.0mg/5ml dose.

Excipients : Each 5ml contains Liquid Maltitol 1.125g, Ethanol (alcohol) 7.3 Vol %

For full list of excipients see section 6.1

3. Pharmaceutical Form

Oral Solution.

4. Clinical Particulars

4.1 Therapeutic Indications

For the night time symptomatic relief of unproductive cough and congestive symptoms associated with colds.

4.2 Posology And Method Of Administration

Posology

Adults, the Elderly and Children over 12 years

3 X 5ml spoonfuls at bedtime. Repeat after 6 hours if required

4.3 Contraindications

Contraindicated in known hypersensitivity to any of the ingredients. Contraindicated in persons under treatment with monoamine oxidase inhibitors or within 2 weeks of discontinuation of MAOI use.

Dextromethorphan, in common with other centrally acting antitussive agents, should not be given to patients in, or at risk of developing, respiratory failure.

Covonia Night Time Formula should not be used in liver dysfunction. It should not be administered to patients where cough is associated with asthma or patients with productive cough.

4.4 Special Warnings And Precautions For Use

Precautions for use

Because of their antimuscarinic properties antihistamines should be used with care in conditions such as closed angle glaucoma, urinary retention, prostatic hyperplasia or pyeloduodenal obstruction. Caution should also be exercised in patients with epilepsy or severe cardiovascular disorders. Caution is needed for the use of dextromethorphan in patients with a history of asthma.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

It also contains 7.3vol% ethanol (alcohol), i.e. up to 870mg per dose, equivalent to 22ml of beer or 9ml of wine per dose.

Harmful if suffering from alcoholism.

Special warnings

If symptoms persist consult your doctor.

Keep out of the reach and sight of children.

Do not exceed the stated dose.

Causes drowsiness which may continue the next day. If affected to not drive or operate machinery.

Avoid alcoholic drink.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Dextromethorphan should not be used in persons under treatment with monoamine oxidase inhibitors or within 2 weeks of discontinuation of MAOI use in view of the potential risk of a severe or fatal interaction. Cimetidine inhibits the metabolism of opioid analgesics.

Diphenhydramine has additive sedative effects with alcohol and other CNS depressants. It may also have additive antimuscarinic effects with antimuscarinic drugs.

4.6 Pregnancy And Lactation

Although dextromethorphan and diphenhydramine have been in widespread use for many years, insufficient data are available on their use during pregnancy. Use during pregnancy is inadvisable unless there is a clear need. Caution should, therefore, be exercised by balancing the potential benefits of treatment against any possible hazards.

It is not known if dextromethorphan or its metabolites are excreted in human breast milk. Diphenhydramine is excreted in breast milk but the amount has not been quantified. Covonia Night Time Formula is, therefore, best avoided during breast feeding.

4.7 Effects On Ability To Drive And Use Machines

Diphenhydramine may cause drowsiness, persons so affected should be advised not to drive or to operate machinery.

4.8 Undesirable Effects

Side-effects are uncommon with dextromethorphan. Rarely, drowsiness, nausea, vomiting, dizziness and gastro-intestinal disturbances may occur.

The most common effects of diphenhydramine are drowsiness and a lowered ability to concentrate. Other effects include dizziness, nausea, nervousness, ataxia, abnormal vision, tremor and vomiting. Antimuscarinic effects may include dry mouth, thickened mucous secretions, palpitations and urinary tract dysfunction. Administration of antihistamines has also been associated with rash, angioedema, convulsions and paresthesias.

4.9 Overdose

Acute overdose of dextromethorphan does not usually result in serious signs and symptoms unless very large amounts have been ingested. Signs and symptoms of substantial overdose may include nausea and vomiting, CNS disturbances (hyperexcitability, irritability, mental confusion, lethargy, somnolence, ataxia, auditory and visual hallucinations), nystagmus and respiratory depression.

Mild cases of diphenhydramine overdose are mainly characterised by prominent antimuscarinic effects including dry mouth, headache, nausea, tachycardia and urinary retention. Larger doses produce depression or stimulation of the CNS. In small children, the stimulatory effects predominate and clinical features include hallucinations and convulsions. Adults usually develop drowsiness first, then convulse and lapse into coma at later stage. Fever and flushing is seen in children but is uncommon in adults.

Gastric lavage should be used if indicated. Naloxone has been used successfully as a specific antagonist to dextromethorphan toxicity in children. Convulsions can be controlled with diazepam. Other treatment is supportive and symptomatic and may include artificial respiration, external cooling for hyperpyrexia and intravenous fluids.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC Code: RO5 DA – Opium Alkaloids and Derivatives

Dextromethorphan

Dextromethorphan is a non-opioid, centrally acting cough suppressant. It raises the threshold for the cough reflex in the medulla oblongata. In therapeutic doses, it has no significant analgesic, respiratory depressant, euphoriant or dependence-producing properties. It does not inhibit ciliary function.

Diphenhydramine

Diphenhydramine is an ethanolamine H₁ histamine receptor antagonist. It possesses antitussive, sedative, antimuscarinic and antiemetic properties. Antihistamines, like diphenhydramine, are useful for controlling nasal itching, sneezing and rhinorrhoea but are less effective for the relief of nasal congestion.

5.2 Pharmacokinetic Properties

Dextromethorphan

Dextromethorphan is rapidly absorbed from the gastrointestinal tract following oral administration. It is subject to extensive presystematic metabolism resulting in very low peak plasma concentrations of 1.8ng/ml within 2.5 hours of an oral dose. Peak concentrations of the main metabolite, dextrophan occur 1-2 hours after ingestion. The terminal plasma elimination half-life of dextrophan is about three hours.

It is not known if dextromethorphan or dextrophan is excreted into breast milk or crosses the placenta.

Dextromethorphan is extensively metabolised in the liver. It is mainly metabolised to dextrophan by O-demethylation involving the cytochrome P45011D6 isozyme, which is then conjugated by UDP-glucuronosyl transferases. Up to 9% of individuals have been found to be poor metabolisers and the half-life of dextromethorphan may be extremely prolonged in these people.

Less than 1% of the dose of dextromethorphan is excreted in the faeces. Urinary excretion of parent drug and metabolites accounts for up to 50% of the ingested dose over 24 hours.

Diphenhydramine

Diphenhydrainine is well absorbed from the gastrointestinal tract but its availability varies between 26 and 60% due to first pass metabolism. Peak plasma concentrations are achieved about 1 to 4 hours after oral administration. The plasma elimination half-life is 3.3 hours.

Diphenhydramine is widely distributed throughout the body including the CNS. It crosses the placenta and has been detected in breast milk. It is highly (85-98%) bound to plasma proteins.

Orientals have lower plasma levels, lower protein binding and a higher volume of distribution and higher plasma clearance, but not half-life, than Caucasians.

Diphenhydramine is extensively metabolised mainly in the liver. It is N-demethylated to monodesmethyldiphenhydramine and didesmethyldiphenhydramine. The resultant primary amine is oxidatively deaminated to yield the carboxylic acid, diphenylmethoxy acetic acid which may be conjugated with glutamine or glycine.

Diphenhydramine is excreted mainly in the urine with very little excreted as unchanged drug.

5.3 Preclinical Safety Data

Dextromethorphan

A 13 weeks dietary study in rats has shown no evidence of toxicity at the 0.1mg/kg dextromethorphan level. Dextromethorphan has been reported to have no mutagenic potential in two species and no effect on perinatal or postnatal mortality in high doses.

Diphenhydramine

In the rat, administration of 12mg/kg i.p. diphenhydramine hydrochloride has been reported to produce foetal mortality and mortality in the offspring up to the tenth day after birth. Doses up to 20 and 25 times the human dose (on a mg/kg basis) exert no teratogenic effects in rats and rabbits.

There is no evidence for diphenydramine being mutagenic or carcinogenic in man.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium Benzoate

Ethanol (96%)

Hydroxyethylcellulose. (Natrosol G PH).

Povidone K30.

Glycerol.

Liquid Sorbitol Non-Crystallising.

Liquid Maltitol

Saccharin Sodium.

Capsicum Tincture.

Menthol.

Peppermint Oil.

Anise Oil.

Citric Acid Monohydrate.

Macrogol Cetostearyl Ether

Caramel.

Blackcurrant Flavour 1122267 – containing propylene glycol.

6.2 Incompatibilities

None.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 25°C. Protect from light.

6.5 Nature And Contents Of Container

150ml amber soda glass bottle with 28mm tamper evident child resistant closure with EPE/ Saranex liner.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Thornton & Ross Ltd.

Linthwaite Laboratories

Huddersfield

HD7 5QH.

8. Marketing Authorisation Number(S)

PL: 00240/0042

9. Date Of First Authorisation/Renewal Of The Authorisation

23.09.97

10. Date Of Revision Of The Text

04/05/2010

tipranavir

tye-PRAN-a-vir

Oral route(Capsule;Solution)

Clinical hepatitis and hepatic decompensation, including some fatalities, have been reported. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C coinfection. Fatal and nonfatal intracranial hemorrhage have also been reported .

Commonly used brand name(s)

In the U.S.

• Aptivus

Available Dosage Forms:

• Solution


• Capsule, Liquid Filled

Therapeutic Class: Antiviral

Pharmacologic Class: Protease Inhibitor

Uses For tipranavir

Tipranavir is used in combination with ritonavir (Norvir®) to treat an infection caused by the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS). tipranavir is usually given to patients who have received HIV treatment in the past.

Tipranavir will not cure or prevent HIV infection or AIDS. It helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay the development of problems usually related to AIDS or HIV disease from occurring. Tipranavir will not keep you from spreading HIV to other people. People who receive tipranavir may continue to have the problems usually related to AIDS or HIV disease.

tipranavir is available only with your doctor's prescription.

Before Using tipranavir

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 tipranavir, the following should be considered:

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of tipranavir in children younger than 2 years of age. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of tipranavir have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving tipranavir.

Pregnancy

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

Breast Feeding

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

Interactions with Medicines

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

• Alfuzosin


• Amiodarone


• Astemizole


• Bepridil


• Cisapride


• Colchicine


• Dihydroergotamine


• Ergonovine


• Ergotamine


• Flecainide


• Lovastatin


• Methylergonovine


• Midazolam


• Pimozide


• Propafenone


• Quinidine


• Rifampin


• Sildenafil


• Simvastatin


• St John's Wort


• Terfenadine


• Triazolam

Using tipranavir 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.

• Atazanavir


• Atorvastatin


• Bosentan


• Etravirine


• Fluticasone


• Fosamprenavir


• Garlic


• Indinavir


• Lopinavir


• Nelfinavir


• Rifabutin


• Salmeterol


• Saquinavir

Using tipranavir 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.

• Abacavir


• Aluminum Carbonate, Basic


• Aluminum Hydroxide


• Aluminum Phosphate


• Bupropion


• Calcium Carbonate


• Clarithromycin


• Conjugated Estrogens


• Dihydroxyaluminum Aminoacetate


• Dihydroxyaluminum Sodium Carbonate


• Enfuvirtide


• Esterified Estrogens


• Estradiol


• Estriol


• Estrone


• Estropipate


• Ethinyl Estradiol


• Fluconazole


• Magaldrate


• Magnesium Carbonate


• Magnesium Hydroxide


• Magnesium Oxide


• Magnesium Trisilicate


• Methadone


• Omeprazole


• Phenobarbital


• Tadalafil


• Tenofovir Disoproxil Fumarate


• Trazodone


• Zidovudine

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Bleeding problems (e.g., hemophilia)—Use with caution. May increase the chance of bleeding.

• Diabetes mellitus or


• Hyperglycemia (high blood sugar)—May increase the amount of sugar in your blood.

• Hyperlipidemia (high cholesterol or fats in the blood) or


• Liver problems (including hepatitis B or C)—Use with caution. May make these conditions worse. .

• Liver disease, moderate or severe—Should not be used in patients with this condition.

• Sulfa allergy, known or suspected—Use with caution. May cause side effects to be worse.

Proper Use of tipranavir

Take tipranavir exactly as directed by your doctor. Do not change your dose or stop using tipranavir without checking first with your doctor. When your supply of tipranavir is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of tipranavir.

tipranavir comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

Tipranavir is always taken with ritonavir (Norvir®). Take these two medicines at the same time, unless your doctor tells you otherwise.

If you are using tipranavir with ritonavir capsules or oral liquid, you may take it with or without food. However, you should take tipranavir with food if you are using it with ritonavir tablets.

Swallow the capsule whole. Do not break, crush, or chew it.

Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Dosing

The dose of tipranavir 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 tipranavir. 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 treatment of HIV infection:
  
  • For oral dosage forms (capsules or oral liquid):
    
    • Adults—500 milligrams (mg) or 5 milliliters (mL) of tipranavir and 200 mg of ritonavir (Norvir®) two times per day.
    
    
    • Children 2 to 18 years of age—Dose is based on body weight or body size and must be determined by your doctor. The dose is usually 14 milligrams (mg) per kilogram (kg) of body weight of tipranavir plus 6 mg per kg of body weight of ritonavir (Norvir®), or 375 mg/m(2) of body size of tipranavir plus 150 mg/m(2) of body size of ritonavir two times per day. Your doctor may adjust your dose if needed. However, the dose should not be more than the recommended adult dose.
    
    
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of tipranavir, 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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Store the capsules in the refrigerator until you are ready to open the bottle. Once you have opened the medicine bottle, you may store it at room temperature, away from heat, light, or moisture. The medicine is good for up to 60 days after you open the bottle. Throw away any unused capsules after 60 days and get a new bottle of medicine. .

Store the oral liquid at room temperature. Do not refrigerate or freeze it. The liquid must be used within 60 days after you open the bottle.

Precautions While Using tipranavir

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

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

You should not use any of the following medicines while you or your child are taking tipranavir. Using these medicines together with tipranavir may increase your chance of having serious medical problems:

• Alfuzosin (Uroxatral®) or


• Amiodarone (Cordarone®, Pacenone®) or


• Bepridil (Vascor®) or


• Cisapride (Propulsid®) or


• Ergot medicines (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine, Cafergot®, Methergine®, or Migranal®) or


• Flecainide (Tambocor®) or


• Lovastatin (Altocor®, Mevacor®) or


• Oral midazolam (Versed®) or


• Pimozide (Orap®) or


• Propafenone (Rythmol®) or


• Quinidine (Cardioquin®, Quinaglute dura®) or


• Rifampin (Rifadin®, Rimactane®) or


• Sildenafil (Revatio®) or


• Simvastatin (Simcor®, Vytorin®, Zocor®) or


• Triazolam (Halcion®).

tipranavir may decrease the effects of some oral contraceptives (birth control pills). To keep from getting pregnant, use an additional form of birth control with your pills. Other forms include condoms, diaphragms, or contraceptive foams or jellies.

tipranavir may cause intracranial hemorrhage (bleeding in the brain). Make sure your doctor knows if you or your child have a bleeding disorder, or any medical condition that increases your chance of bleeding. Call your doctor right away if you have any unusual or unexplained bleeding.

Stop using tipranavir and check with your doctor right away if you or your child have pain in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

When you start taking HIV medicines, your immune system may get stronger. If you have certain infections that are hidden in your body, such as pneumonia or tuberculosis, you or your child may notice new symptoms when your body tries to fight them. If this occurs, tell your doctor right away.

tipranavir will not keep you from giving HIV to your partner during sex. Make sure you understand and practice safe sex, even if your partner also has HIV. Do not share needles with anyone.

Serious skin reactions can occur with tipranavir. Stop using tipranavir and check with your doctor right away if you or your child have more than one of the following symptoms while using tipranavir: blistering, peeling, or loosening of the skin; fever or chills; itching; joint or muscle pain; severe rash; red skin lesions; sunburn; throat tightness; or sores, ulcers, or white spots in the mouth or on the lips.

tipranavir may make your skin more sensitive to sunlight. Use a sunscreen when you are outdoors. Wear protective clothing and hats. Avoid sunlamps and tanning beds.

tipranavir may cause you to have excess body fat. Tell your doctor if you or your child notice changes in your body shape, such as an increased amount of fat in the upper back and neck, or around the chest and stomach area; or a loss of fat from the legs, arms, and face.

tipranavir Side Effects

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

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

Less common

• Bleeding gums


• confusion


• cough producing mucus


• coughing up blood


• difficulty with breathing or swallowing


• dizziness


• fever


• general feeling of tiredness or weakness


• headache


• increased menstrual flow or vaginal bleeding


• loss of appetite


• nausea or vomiting


• nosebleeds


• paralysis


• prolonged bleeding from cuts


• red or black, tarry, or light-colored stools


• red or dark brown urine


• shortness of breath


• sudden severe weakness


• tightness in the chest


• unusual bleeding


• upper right abdominal or stomach pain


• wheezing


• yellow eyes and skin

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

• Diarrhea

Less common

• Abdominal or stomach pain


• cough


• discouragement


• fat redistribution


• feeling sad or empty


• irritability


• lack of appetite


• lack or loss of strength


• loss of interest or pleasure


• rash


• sleeplessness


• trouble concentrating


• trouble sleeping


• unable to sleep

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: tipranavir 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 tipranavir resources

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

• Tipranavir Professional Patient Advice (Wolters Kluwer)


• Tipranavir Monograph (AHFS DI)


• Tipranavir MedFacts Consumer Leaflet (Wolters Kluwer)


• Aptivus Prescribing Information (FDA)


• Aptivus Consumer Overview

Compare tipranavir with other medications

• HIV Infection

Tambocor Tablets

Tambocor 50 mg & 100 mg Tablets

Flecainide acetate

Read all of this leaflet carefully before you take this medicine.

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


• If you have any further questions, ask your doctor or nurse.


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

In this leaflet:

• 1. What Tambocor tablets are for


• 2. Before you take Tambocor tablets


• 3. How to take Tambocor tablets


• 4. Possible side effects


• 5. How to store Tambocor tablets


• 6. Further information.

What Tambocor tablets are for

Tambocor tablets belong to a group of medicines called anti-arrhythmics. Anti-arrhythmics work by controlling the rate and rhythm of the heart.

Tambocor tablets are used to treat:

• Arrhythmias (irregular heart beat)


• Tachycardia (heart beat too fast)


• Atrial fibrillation (rapid contractions of muscles in the heart).

It is important for your doctor to treat these conditions quickly and effectively in order to prevent more serious heart problems from developing.

There are two strengths of tablet available, 50 mg and 100 mg.

Before you take Tambocor tablets

Do not take Tambocor tablets if:

• You are allergic to flecainide acetate or any of the other ingredients of Tambocor tablets (see Section 6)


• You have heart failure


• You have heart block (your heart misses beats)


• You have long-standing atrial fibrillation (rapid contractions of muscles in the heart)


• You have or have ever had any heart problems including problems with the valves in your heart or conduction problems


• You have sinus node dysfunction (a specific condition where your heart beats abnormally)


• You have had a myocardial infarction (heart attack)


• You are pregnant or breast-feeding.

Tambocor tablets are not recommended for use in children under 12 years of age.

If any of the above applies to you tell your doctor or nurse.

Before you take Tambocor tablets your doctor or nurse may check:

• Your fluid levels are correct


• Your liver and kidney functions.

This is to check that Tambocor tablets are right for you and to help the doctor calculate the dose you need.

Check with your doctor or nurse before taking Tambocor tablets if:

• You have high blood pressure


• You have angina (chest pains)


• You have heart disease


• You have kidney disease or kidney problems


• You have liver disease or liver problems


• You wear a pacemaker.

Tell your doctor or nurse if you are taking any of the following medicines:

• Any other medicine used to treat heart arrhythmias or heart problems such as cardiac glycosides, beta-blockers, verapamil or amiodarone


• Medicines to treat high blood pressure


• Antidepressants (medicines used to treat depression), such as tricyclic antidepressants, Prozac, fluoxetineor reboxetine


• Anticonvulsants (medicines used to prevent epileptic fits) such as phenytoin, phenobarbital or carbamazepine


• Antipsychotics (medicines to treat mental illness) such as clozapine


• Antihistamines (medicines to treat allergic reactions) such as mizolastine or terfenadine


• Quinine (medicine to treat malaria)


• Medicines to treat HIV such as ritonavir, lopinavir or indinavir


• Diuretics (water tablets)


• Cimetidine (medicine to treat stomach ulcers)


• Bupropion (a medicine to help stop you smoking)


• Any other medicine, including medicines obtained without a prescription.

These medicines may interfere with your treatment.

Pregnancy and breast-feeding

If you are pregnant, trying to become pregnant or breast-feeding, ask the doctor or nurse for advice before taking Tambocor tablets.

How to take Tambocor tablets

Always take Tambocor tablets exactly as your doctor has told you.

Important:

Your doctor will choose the dose that is right for your condition. Usually your treatment with Tambocor tablets will be started in hospital.

Adults:

Supraventricular arrhythmias (Irregular heart beat that starts in the upper chambers of your heart)

• Tambocor 50mg tablets: The usual dose is one tablet twice a day.


• Tambocor 100mg tablets: The usual dose is half a tablet twice a day.

Your doctor may prescribe up to a total dose of 300 mg daily (3 x 100 mg tablets or 6 x 50 mg tablets).

Ventricular arrhythmias (Irregular heart beat that starts in the lower chambers of your heart)

• Tambocor 50mg tablets: The usual dose is two tablets twice a day.


• Tambocor 100mg tablets: The usual dose is one tablet twice a day

Your doctor may prescribe up to a total dose of 400 mg daily (4 x 100 mg tablets or 8 x 50 mg tablets).

The elderly and patients with kidney or heart problems:

• For elderly patients, and patients with kidney or heart problems, the doctor may tell you to take a lower dose.

While you are taking this medicine, your doctor may ask you to have check-ups. These are to make sure that your medicine is working properly and that the dose you are taking is right for you.

Children:

• Tambocor tablets are not recommended for children under 12 years of age.

If you take more Tambocor tablets than you should

If you accidentally take too much, immediately go to the nearest hospital casualty department.

If you forget to take Tambocor tablets

Do not take a double dose to make up for a missed dose. Simply take the next dose as planned.

If you stop taking Tambocor tablets

Do not stop taking Tambocor tablets without first talking to your doctor.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

Tambocor Tablets Side Effects

Like all medicines Tambocor tablets can cause side effects, although not everybody gets them.

Seek immediate medical help if you have any of the following symptoms:

• Your heartbeat changes; it starts to pound, or it gets faster or slower


• You have chest pain


• You become breathless or have other breathing problems


• You faint or you feel faint


• You have ringing in your ears


• Your skin and eyes begin to go yellow (jaundice)


• You have a fever, become flushed or sweat


• You have fits (convulsions).

Other side effects:

• Feeling or being sick


• Constipation


• Feeling bloated


• Wind


• Diarrhoea


• Stomach pain or indigestion


• Loss of appetite


• Confusion and hallucinations


• Forgetfulness


• Difficulty sleeping


• Feeling anxious (worried)


• Depression


• Red, itchy or swollen skin rash


• Hair loss


• Sensitivity to sunlight


• Feeling weak or tired


• Headache


• Double or blurred vision


• Small cloudy spots on the eyeball


• Feeling giddy or lightheaded


• Dizziness or feeling that the room is spinning (vertigo)


• Shaking (tremors)


• Unsteady walking, uncontrolled movements or poor coordination


• Numb or tingling hands or feet


• Swelling.

If any of these side effects get serious, or you notice any side effects not listed in this leaflet, tell your doctor or nurse.

How to store Tambocor tablets

Keep out of the reach and sight of children.

Do not store above 30°C.

Keep the container in the outer carton to protect the tablets from light.

Do not use Tambocor tablets after the expiry date on the carton. The expiry date refers to the last day of that month. Medicines should not be disposed of via wastewater or household waste. Return any medicine you no longer need to your pharmacist.

Further information

What Tambocor tablets contain

• The active substance in Tambocor tablets is flecainide acetate. Each 50 mg tablet contains 50 mg of flecainide acetate. Each 100 mg tablet contains 100 mg flecainide acetate.



• The other ingredients are pregelatinised starch, croscarmellose sodium, microcrystalline cellulose (E460i), hydrogenated vegetable oil, magnesium stearate (E572).

What Tambocor tablets look like

Tambocor 50 mg tablets are round, white and marked ‘3M’ on one side and ‘TR50’ on the other.

Tambocor 100 mg tablets are round, white and marked ‘3M’ on one side and ‘TR100’ with a break line on the other.

Both strengths of Tambocor tablets come in blister packs containing 60 tablets.

Marketing Authorisation Holder:

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop’s Stortford

CM22 6PU

UK

Manufacturer:

3M Health Care Limited

1 Morley Street

Loughborough

Leicester

LE11 1EP

UK

This leaflet was last updated December 2009

If this leaflet is difficult to see or read and you would like it in a different format, please contact

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop’s Stortford
CM22 6PU

UK

562197M6210UK00

6204 1370 4

Tambocor is a trademark of MEDA AB.

The Triangle Logo on the packaging is a trademark of 3M and is used under license.