Ticlid
Ticlid - General Information
Ticlid is an effective inhibitor of platelet aggregation. The drug has been found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [PubChem]
Pharmacology of Ticlid
Ticlid is a platelet aggregation inhibitor structurally and pharmacologically similar to clopidogrel. When taken orally, ticlopidine causes a time- and dose-dependent inhibition of both platelet aggregation and release of platelet granule constituents, as well as a prolongation of bleeding time. The intact drug has no significant in vitro activity at the concentrations attained in vivo; and, although analysis of urine and plasma indicates at least 20 metabolites, no metabolite which accounts for the activity of ticlopidine has been isolated.
Ticlid for patients
IMPORTANT INFORMATION ABOUT TICLID (ticlopidine HCl) TABLETS
The information in this leaflet is intended to help you use TICLID safely. Please read the leaflet carefully. Although it does not contain all the detailed medical information that is provided to your doctor, it provides facts about TICLID that are important for you to know. If you still have questions after reading this leaflet or if you have questions at any time during your treatment with TICLID, check with your doctor.
Why TICLID was Prescribed by Your Doctor
Stroke Patients: TICLID is recommended to help reduce your risk of having a stroke, but only for patients who have had a stroke or early stroke warning symptoms while on aspirin, or for those who have these symptomsbut are intolerant or allergic to aspirin.
Stent Patients: TICLID is recommended with aspirin for up to 30 days in patients who have had a stent implanted in their coronary arteries to reduce the risk of blood clots forming inside the stent.
Special Warning for Users of TICLID/Necessary Blood Tests: TICLID is not prescribed for those who can take aspirin to reduce the risk of stroke because TICLID can cause life-threatening blood problems. Getting your blood tests done and reporting symptoms to your doctor as soon as possible can avoid serious complications.
The white cells of the blood that fight infection may drop to dangerous levels (a condition called neutropenia). This occurs in about 2.4% (1 in 40) of people on ticlopidine. You should be on the lookout for signs of infection such as fever, chills or sore throat. If this problem is caught early, it can almost always be reversed, but if undetected it can be fatal.
Another problem that has occurred in some patients taking ticlopidine is a decrease in cells called platelets (a condition called thrombocytopenia). This may occur as part of a syndrome that includes injury to red blood cells, causing anemia, kidney abnormalities, neurologic changes and fever. This condition is called TTP and can be fatal.
Things you should watch for as possible early signs of TTP are yellow skin or eye color, pinpoint dots (rash) on the skin, pale color, fever, weakness on a side of the body, or dark urine. If any of these occur, contact your doctor immediately.
Both complications occur most frequently in the first 90 days after TICLID is started. To make sure you don't develop either of these problems, your doctor will arrange to have your blood tested before you start taking TICLID and then every 2 weeks for the first 3 months you are on TICLID. If detected, neutropenia and thrombocytopenia can almost always be reversed. It is essential that you keep your appointments for the blood tests and that you call your doctor immediately if you have any indication that you may have TTP or neutropenia. If you stop taking TICLID for any reason within the first 3 months, you will still need to have your blood tested for an additional 2 weeks after you have stopped taking TICLID.
Rarely, decreases in the white blood cells, red blood cells and platelets can occur together. This condition is called aplastic anemia and can be fatal.
Things you should watch for as possible early signs of aplastic anemia are feeling of excessive weakness and tiredness, paleness, bruising, and bleeding from areas such as your nose or gums. You may also develop signs of infection such as fever. If any of these occur, contact your doctor immediately.
Other Warnings and Precautions: A few people may develop jaundice while being treated with TICLID. The signs of jaundice are yellowing of the skin or the whites of the eyes or consistent darkening of the urine or lightening in the color of the stools. These symptoms should be reported to your physician promptly.
If any of the symptoms described above for neutropenia, TTP, aplastic anemia or jaundice occur, contact your doctor immediately.
TICLID should be used only as directed by your doctor. Do not give TICLID to anyone else. Keep TICLID out of reach of children!
Some people may have such side effects as diarrhea, skin rash, stomach or intestinal discomfort. If any of these problems are persistent, or if you are concerned about them, bring them to your doctor's attention
It may take longer than usual to stop bleeding when taking TICLID. Tell your doctor if you have any more bleeding or bruising than usual, and, if you have emergency surgery, be sure to let your doctor or dentist know that you are taking TICLID. Also, tell your doctor well in advance of any planned surgery (including tooth extraction), because he or she may recommend that you stop taking TICLID temporarily.
How TICLID Works
Stroke Patients: A stroke occurs when a clot (or thrombus) forms in a blood vessel in the brain or forms in another part of the body and breaks off, then travels to the brain (an embolus). In both cases the blood supply to part of the brain is blocked and that part of the brain is damaged. TICLID works by making the blood less likely to clot, although not so much less that it causes you to become likely to bleed, unless you have a bleeding disorder or some injury (such as a bleeding ulcer of the stomach or intestine) that is especially likely to bleed.
Stent Patients: A heart attack or angina (chest pain) can occur when fatty deposits block the arteries that carry oxygen and nutrient-rich blood to your heart. To decrease the chance of fatty deposits building up over time, your doctor may recommend the placement of a coronary stent. TICLID may be given to you with aspirin to make blood clots less likely to form inside the stent so that the artery remains open.
Who Should Not Take TICLID? Contact your doctor immediately and do not take TICLID if:
· you have an allergic reaction to TICLID
· you have a blood disorder or a serious bleeding problem, such as a bleeding stomach ulcer
· you have previously been told you had TTP or aplastic anemia
· you have severe liver disease or other liver problems
· you are pregnant or you are planning to become pregnant
· you are breast-feeding
Ticlid Interactions
Therapeutic doses of TICLID caused a 30% increase in the plasma half-life of antipyrine and may cause analogous effects on similarly metabolized drugs. Therefore, the dose of drugs metabolized by hepatic microsomal enzymes with low therapeutic ratios or being given to patients with hepatic impairment may require adjustment to maintain optimal therapeutic blood levels when starting or stopping concomitant therapy with ticlopidine. Studies of specific drug interactions yielded the following results:
Aspirin and Other NSAIDs: Ticlopidine potentiates the effect of aspirin or other NSAIDs on platelet aggregation. The safety of concomitant use of ticlopidine and NSAIDs has not been established. The safety of concomitantuse of ticlopidine and aspirin beyond 30 days has not been established. Aspirin did not modify the ticlopidine-mediated inhibition of ADP-induced platelet aggregation, but ticlopidine potentiated the effect of aspirin on collagen-induced platelet aggregation. Caution should be exercised in patients who have lesions with a propensity to bleed, such as ulcers. Long-term concomitant use of aspirin and ticlopidine is not recommended.
Antacids: Administration of TICLID after antacids resulted in an 18% decrease in plasma levels of ticlopidine.
Cimetidine: Chronic administration of cimetidine reduced the clearance of a single dose of TICLID by 50%.
Digoxin: Coadministration of TICLID with digoxin resulted in a slight decrease (approximately 15%) in digoxin plasma levels. Little or no change in therapeutic efficacy of digoxin would be expected.
Theophylline: In normal volunteers, concomitant administration of TICLID resulted in a significant increase in the theophylline elimination half-life from 8.6 to 12.2 hours and a comparable reduction in total plasma clearance of theophylline.
Phenobarbital: In 6 normal volunteers, the inhibitory effects of TICLID on platelet aggregation were not altered by chronic administration of phenobarbital.
Phenytoin: In vitro studies demonstrated that ticlopidine does not alter the plasma protein binding of phenytoin. However, the protein binding interactions of ticlopidine and its metabolites have not been studied in vivo. Several cases of elevated phenytoin plasma levels with associated somnolence and lethargy have been reported following coadministration with TICLID. Caution should be exercised in coadministering this drug with TICLID, and it may be useful to remeasure phenytoin blood concentrations.
Propranolol: In vitro studies demonstrated that ticlopidine does not alter the plasma protein binding of propranolol. However, the protein binding interactions of ticlopidine and its metabolites have not been studied in vivo. Caution should be exercised in coadministering this drug with TICLID.
Other Concomitant Therapy: Although specific interaction studies were not performed, in clinical studies TICLID was used concomitantly with beta blockers, calcium channel blockers and diuretics without evidence of clinically significant adverse interactions.
Food Interaction: The oral bioavailability of ticlopidine is increased by 20% when taken after a meal. Administration of TICLID with food is recommended to maximize gastrointestinal tolerance. In controlled trials in stroke patients, TICLID was taken with meals.
Ticlid Contraindications
The use of TICLID is contraindicated in the following conditions:
· Hypersensitivity to the drug
· Presence of hematopoietic disorders such as neutropenia and thrombocytopenia or a past history of either TTP or aplastic anemia
· Presence of a hemostatic disorder or active pathological bleeding (such as bleeding peptic ulcer or intracranial bleeding)
· Patients with severe liver impairment
Additional information about Ticlid
Ticlid Indication: Used to reduce the risk of thrombotic stroke (fatal or nonfatal) in patients who have experienced stroke precursors, and in patients who have had a completed thrombotic stroke.
Mechanism Of Action: The active metabolite of ticlopidine prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of ticlopidine.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Ticlopidine
Synonyms: Ticlopidine HCL; Ticlopidine Hydrochloride
Drug Category: Fibrinolytic Agents; Platelet Aggregation Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Ticlopidine: Ticlid;
Absorption: Absorption is greater than 80%. Food increases absorption.
Toxicity (Overdose): Single oral doses of ticlopidine at 1600 mg/kg and 500 mg/kg were lethal to rats and mice, respectively. Symptoms of acute toxicity were GI hemorrhage, convulsions, hypothermia, dyspnea, loss of equilibrium and abnormal gait.
Protein Binding: Binds reversibly (98%) to plasma proteins, mainly to serum albumin and lipoproteins. The binding to albumin and lipoproteins is nonsaturable over a wide concentration range. Ticlopidine also binds to alpha-1 acid glycoprotein. At concentrations attained with the recommended dose, only 15% or less ticlopidine in plasma is bound to this protein.
Biotransformation: Metabolized extensively by the liver; only trace amounts of intact drug are detected in the urine. At least 20 metabolites have been identified. It has been proposed that 1 or more active metabolites may account for ticlopidine's activity, because ticlopidine itself is an extremely weak platelet aggregation inhibitor in vitro at the concentrations achieved in vivo. However, no active metabolite has been identified.
Half Life: Half-life following a single 250-mg dose is approximately 7.9 hours in subjects 20 to 43 years of age and 12.6 hours in subjects 65 to 76 years of age. With repeated dosing (250 mg twice a day), half-life is about 4 days in subjects 20 to 43 years of age and about 5 days in subjects 65 to 76 years of age.
Dosage Forms of Ticlid: Tablet Oral
Chemical IUPAC Name: 5-[(2-chlorophenyl)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridine
Chemical Formula: C14H14ClNS
Ticlopidine on Wikipedia: https://en.wikipedia.org/wiki/Ticlopidine
Organisms Affected: Humans and other mammals