Ticlid

ADP (adenosine Diphosphate) Receptor Antagonist Platelet Aggregation Inhibitors

Ticlopidine is administered with food to maximize GI absorption and minimize GI irritation.
Do not give at the same time as antacids.
Because of the risk of life-threatening blood dyscrasias (see Adverse Reactions), ticlopidine should generally be reserved for patients who are intolerant of aspirin.
If there are laboratory signs of thrombotic thrombocytopenia purpura (TTP) or if the neutrophil count falls below 1200/mm3, ticlopidine should be discontinued immediately.

hepatic failure / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
vasculitis / Delayed / 0-1.0
erythema multiforme / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
hepatic necrosis / Delayed / 0-1.0
lupus-like symptoms / Delayed / 0-1.0
peptic ulcer / Delayed / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
nephrotic syndrome / Delayed / 0-1.0
serum sickness / Delayed / 0-1.0
intracranial bleeding / Delayed / 0.5-0.5
aplastic anemia / Delayed / 0-0.1
thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-0.1
agranulocytosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 3.1-7.6
neutropenia / Delayed / 2.4-2.4
hepatitis / Delayed / 0-1.0
cholestasis / Delayed / 0-1.0
pneumonitis / Delayed / 0-1.0
hyponatremia / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
hemolysis / Early / 0-1.0
peripheral neuropathy / Delayed / 0-1.0
colitis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
thrombocytosis / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
platelet dysfunction / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
prolonged bleeding time / Delayed / Incidence not known

diarrhea / Early / 12.5-12.5
dyspepsia / Early / 7.0-7.0
nausea / Early / 7.0-7.0
rash / Early / 5.1-5.1
abdominal pain / Early / 3.7-3.7
purpura / Delayed / 2.2-2.2
vomiting / Early / 1.9-1.9
flatulence / Early / 1.5-1.5
pruritus / Rapid / 1.3-1.3
dizziness / Early / 1.1-1.1
anorexia / Delayed / 1.0-1.0
arthropathy / Delayed / 0-1.0
asthenia / Delayed / 0.5-1.0
headache / Early / 0.5-1.0
tinnitus / Delayed / 0.5-1.0
infection / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
ecchymosis / Delayed / Incidence not known
epistaxis / Delayed / Incidence not known

Ticlopidine is contraindicated in patients with or a history of hematological disease related to hematopoiesis such as neutropenia and thrombocytopenia or a history of agranulocytosis or aplastic anemia, bone marrow suppression, leukemia, neutropenia, pancytopenia, thrombocytopenia, or thrombotic thrombocytopenic purpura (TTP). Similarly, ticlopidine should not be used in patients with bone marrow suppression or leukemia. A reduction in hematopoietic precursors in the bone marrow has been associated with ticlopidine therapy resulting in severe hematologic reactions (see Adverse Reactions). All patients should undergo regular blood tests during therapy. A complete blood count (CBC) should be obtained every 2 weeks for the first 3 months of ticlopidine therapy. If there are laboratory signs of TTP or if the neutrophil count is below 1200/mm3, then ticlopidine should be discontinued immediately. If patients discontinue ticlopidine during the first 3 months, patients should have a complete blood count 2 weeks after stopping therapy due to the prolonged effects of ticlopidine. More frequent monitoring or monitoring after the first 3 months of therapy is only necessary only in patients with clinical (e.g., signs and symptoms of infection) or laboratory signs (e.g., neutrophil count < 70% of the baseline count, anemia, decreased platelet count) of hematologic effects. Ticlopidine is occasionally associated with thrombocytopenia unrelated to aplastic anemia or TTP. Any manifestations, such as an unusual bleeding event, infection in presence of low WBC or platelets, fever, pallor, petechiae or purpura, dark urine, jaundice, or neurological changes, can indicate an adverse hematologic reaction. A simultaneous decrease in platelet count and WBC should prompt further investigation for a diagnosis of aplastic anemia. Because platelet transfusions may accelerate thrombosis in patients with TTP, they should be avoided, if possible.
 

Ticlid

Rx

Oral platelet-aggregation inhibitor; associated with a risk of life-threatening blood dyscrasias; should be reserved for patients who are intolerant or allergic to aspirin therapy or who have failed aspirin therapy.

250 mg PO twice daily.

250 mg PO twice daily with antiplatelet doses of aspirin for up to 30 days following successful stent implantation. Ticlopidine 250 mg PO twice daily plus aspirin was studied in a comparison of antiplatelet and anticoagulation therapy in patients undergoing placement of a coronary artery stent following percutaneous transluminal coronary angiography (i.e., ticlopidine plus aspirin was compared to phenprocoumon plus aspirin). Cardiac events and hemorrhagic complications were both lower in the ticlopidine-aspirin group.

In 1 small study, 43 patients with acute myocardial infarction were randomized to ticlopidine 250 mg PO twice daily or placebo within 12 hours of onset of chest pain. Ticlopidine was continued for 3 months post-myocardial infarction. Infarct size was significantly reduced in the ticlopidine group.

A dose of 250 mg PO twice daily was recommended by the American College of Chest Physicians (2001 Consensus Conference) for patients with aspirin allergy or intolerance. A dose of 250 mg PO twice daily was compared to "conventional treatment" in 652 patients with unstable angina. Intention-to-treat analysis yielded a 46.6% reduction in risk of vascular death and nonfatal myocardial infarction. Fatal and nonfatal myocardial infarction occurred in 10.9% of the control group and 5.1% of the ticlopidine group.

250 mg PO twice daily. The efficacy of ticlopidine for improving maximum walking distance in patients with intermittent claudication are inconclusive; however, ticlopidine may be an option for some patients who have failed or not tolerated other therapies.

Ticlopidine 250 mg PO twice daily has been evaluated in patients with intermittent claudication to see if it reduces the incidence of myocardial infarction (MI), stroke, and/or transient ischemic attacks. The mortality rate was significantly lower in the ticlopidine group and this observation was mainly accounted for by reduced mortality from ischemic heart disease. Although this study analyzed both cardiac and cerebrovascular events simultaneously, it suggests that ticlopidine may be considered a viable alternative to aspirin for MI prophylaxis.

Several studies have demonstrated the ability of ticlopidine to prevent occlusion within a coronary artery bypass graft. In 1 study, ticlopidine 250 mg PO twice daily, started on the second day after surgery, lowered the rate of graft occlusion at day 10 and after 12 months compared to placebo.

In 1 study, ticlopidine 250 mg PO twice daily was compared to placebo to reduce the progression of diabetic retinopathy. The mean yearly progression in the number of definite microaneurysms was significantly reduced by ticlopidine.

In 1 trial, patients were randomized to ticlopidine 250 mg PO twice daily or placebo for 6 months. Ticlopidine significantly reduced the number of sickle cell crises by 66.4%.

†Indicates off-label use

No specific guidelines are available. Ticlopidine is extensively metabolized by the liver and dosage reductions may be needed in patients with moderate hepatic impairment; initiate the adult dosage cautiously and monitor clinical response. Ticlopidine is contraindicated in patients with severe hepatic disease, who may have bleeding diatheses.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abciximab: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Abrocitinib: (Contraindicated) Concurrent use with ticlopidine is contraindicated during the first 3 months of abrocitinib therapy due to an increased risk of bleeding with thrombocytopenia. After 3 months of abrocitinib therapy, do not exceed a dose of 100 mg PO once daily if coadministered with ticlopidine. Concurrent use may increase the combined exposure of abrocitinib and its 2 active metabolites; monitor closely for adverse reactions. Abrocitinib is a CYP2C19 substrate and ticlopidine is a strong CYP2C19 inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Acetaminophen; Aspirin: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of platelet inhibitors with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors.
Altretamine: (Moderate) An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as altretamine.
Aminolevulinic Acid: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine.
Antacids: (Major) Administration of ticlopidine after antacids resulted in an 18% decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Antithrombin III: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Antithymocyte Globulin: (Moderate) An increased risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia, such as antithymocyte globulin. Platelet inhibitors should be used cautiously in patients with thrombocytopenia following the administration of antithymocyte globulin or other drugs that cause significant thrombocytopenia due to the increased risk of bleeding.
Apixaban: (Major) The concomitant use of apixaban and platelet inhibitors (e.g, aspirin) may increase the risk of bleeding. In the ARISTOTLE trial (comparative trial of apixaban and warfarin in patients with nonvalvular atrial fibrillation), concomitant use of aspirin increased the bleeding risk of apixaban from 1.8%/year to 3.4%/year. If given concomitantly, patients should be educated about the signs and symptoms of bleeding and be instructed to report them immediately or go to an emergency room.
Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g., clopidogrel, platelet glycoprotein IIb/IIIa inhibitors, ticlopidine, etc.) in combination with argatroban.
Arsenic Trioxide: (Moderate) Ticlopidine therapy is contraindicated in patients with hematopoietic disorders including myelosuppression and thrombocytopenia. Ticlopidine should be used cautiously, if at all, in patients with thrombocytopenia following the administration of myelosuppressive antineoplastic agents due to a potential increase in the risk of bleeding.
Aspirin, ASA: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Caffeine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Carisoprodol: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy. (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as ticlopidine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy. (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as ticlopidine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction. (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine. (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Omeprazole: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Aspirin, ASA; Oxycodone: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of ticlopidine with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and ticlopidine is a CYP2C19 inhibitor.
Bendamustine: (Major) Consider the use of an alternative therapy if ticlopidine treatment is needed in patients receiving bendamustine. Ticlopidine may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and ticlopidine is a CYP1A2 inhibitor.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and platelet inhibitors are used concomitantly. Coadministration of betrixaban and platelet inhibitors may increase the risk of bleeding.
Bexarotene: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including bexarotene.
Bivalirudin: (Moderate) When used as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI), bivalirudin is intended for use with aspirin (300 to 325 mg/day PO) and has been studied only in patients receiving concomitant aspirin. Generally, an additive risk of bleeding may be seen in patients receiving other platelet inhibitors (other than aspirin). In clinical trials in patients undergoing PTCA, patients receiving bivalirudin with heparin, warfarin, or thrombolytics had increased risks of major bleeding events compared to those receiving bivalirudin alone. According to the manufacturer, the safety and effectiveness of bivalirudin have not been established when used in conjunction with platelet inhibitors other than aspirin. However, bivalirudin has been safely used as an alternative to heparin in combination with provisional use of platelet glycoprotein IIb/IIIa inhibitors during angioplasty (REPLACE-2). In addition, two major clinical trials have evaluated the use of bivalirudin in patients receiving streptokinase following acute myocardial infarction (HERO-1, HERO-2). Based on the these trials, bivalirudin may be considered an alternative to heparin therapy for use in combination with streptokinase for ST-elevation MI. Bivalirudin has not been sufficiently studied in combination with other more specific thrombolytics.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and ticlopidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticlopidine inhibits CYP1A2.
Bupropion: (Moderate) Ticlopidine is a potent inhibitor of CYP2B6. By inhibiting this isoenzyme, ticlopidine theoretically could increase the plasma concentrations of drugs that are metabolized by CYP2B6, such as bupropion. Adverse reactions of bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures, may be more likely to occur.
Bupropion; Naltrexone: (Moderate) Ticlopidine is a potent inhibitor of CYP2B6. By inhibiting this isoenzyme, ticlopidine theoretically could increase the plasma concentrations of drugs that are metabolized by CYP2B6, such as bupropion. Adverse reactions of bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures, may be more likely to occur.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Calcium Carbonate: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Calcium Carbonate; Magnesium Hydroxide: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Calcium Carbonate; Simethicone: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Calcium; Vitamin D: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Carbamazepine: (Minor) Neurological toxicity and increased carbamazepine serum concentrations have been reported in a coronary stent patient treated with ticlopidine. This potential interaction requires further evaluation.
Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as ticlopidine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
Chlorambucil: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as chlorambucil.
Cilostazol: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of cilostazol and ticlopidine. Both agents are platelet inhibitors; therefore, concomitant use may increase the risk of bleeding. Additionally, ticlopidine may increase serum concentrations of cilostazol. Cilostazol is a CYP2C19 substrate and ticlopidine is a potent CYP2C19 inhibitor. Platelet aggregation returns to normal within 96 hours of discontinuing cilostazol.
Cimetidine: (Major) Cimetidine has been shown to reduce the clearance of ticlopidine by 50%. Monitor for increased ticlopidine-related adverse effects during concurrent use.
Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with ticlopidine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. In addition, platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., ticlopidine). Patients should be instructed to monitor for signs and symptoms of citalopram-related adverse events and bleeding while taking an SSRI concurrently with ticlopidine and to promptly report any bleeding events to the practitioner.
Cladribine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of ticlopidine. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and ticlopidine is a potent inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
Clofarabine: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clopidogrel: (Moderate) Because clopidogrel inhibits platelet aggregation, a potential additive risk for bleeding exists if clopidogrel is given in combination with other drugs that affect hemostasis such as platelet inhibitors. Also, coadministration of clopidogrel and ticlopidine should be avoided. Ticlopidine and clopidogrel inhibit platelets via the same mechanism; combination therapy would therefore be duplicative and not recommended. Furthermore, ticlopidine is a CYP2C19 inhibitor, and clopidogrel requires hepatic biotransformation via CYP2C19 to its active metabolite. When clopidogrel is coadministered with other potent CYP2C19 inhibitors, the plasma concentration and platelet inhibition activity of clopidogrel are reduced. Coadministration of clopidogrel and ticlopidine would be expected to have a similar effect and should be avoided.
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking platelet inhibitors is advised. The efficacy and safety of administering injectable collagenase to a patient taking a platelet inhibitor within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
Cyclosporine: (Moderate) Ticlopidine decreases cyclosporine concentrations. It is prudent to monitor cyclosporine concentrations if ticlopidine therapy is initiated or discontinued.
Dabigatran: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Dalteparin: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Dasatinib: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and ticlopidine is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Desirudin: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
Dextromethorphan; Bupropion: (Moderate) Ticlopidine is a potent inhibitor of CYP2B6. By inhibiting this isoenzyme, ticlopidine theoretically could increase the plasma concentrations of drugs that are metabolized by CYP2B6, such as bupropion. Adverse reactions of bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures, may be more likely to occur.
Digoxin: (Minor) Ticlopidine has been shown to slightly decrease digoxin plasma levels. The magnitude of this pharmacokinetic interaction may not be clinically significant.
Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as ticlopidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Duloxetine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
Edoxaban: (Major) Coadministration of edoxaban and platelet inhibitors should be avoided due to an increased risk of bleeding during concurrent use. Occasionally, short-term coadministration may be necessary in patients transitioning to and from edoxaban. Long-term coadminstration is not recommended. Promptly evaluate any signs or symptoms of blood loss in patients on concomitant therapy.
Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including ticlopidine, before initiation of enoxaparin therapy. If a patient is switched from an anticoagulant to ticlopidine, discontinue the anticoagulant prior to ticlopidine administration. If coadministration is essential, conduct close clinical and laboratory monitoring.
Eptifibatide: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with ticlopidine, a CYP2C19 inhibitor. In addition, platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., ticlopidine). Patients should be instructed to monitor for signs and symptoms of escitalopram-related adverse events and bleeding while taking an SSRI concurrently with ticlopidine and to promptly report any bleeding events to the practitioner.
Esomeprazole: (Minor) Ticlopidine may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as esomeprazole.
Ethotoin: (Moderate) Ticlopidine is an inhibitor of the hepatic isoenzyme CYP2C19 and has been shown to reduce the clearance of phenytoin in patients previously on a stable phenytoin dosage regimen. Hydantoin dosage adjustments may be necessary in some patients who receive ticlopidine concurrently.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and ticlopidine is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; ticlopidine is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Fludarabine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Fluoxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., ticlopidine). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Fluvoxamine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Fondaparinux: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Fosphenytoin: (Moderate) Ticlopidine is an inhibitor of the hepatic isoenzyme CYP2C19 and has been shown to reduce the clearance of phenytoin in patients previously on a stable phenytoin dosage regimen. Hydantoin dosage adjustments may be necessary in some patients who receive ticlopidine concurrently.
Garlic, Allium sativum: (Moderate) Use together with caution. Garlic produces clinically significant antiplatelet effects, and a risk for bleeding may occur if platelet inhibitors are given in combination with garlic.
Ginger, Zingiber officinale: (Moderate) Ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist so additive bleeding may occur if platelet inhibitors are given in combination with ginger, zingiber officinale.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and platelet inhibitors as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if co administered with aspirin. Caution and careful monitoring of clinical and/or laboratory parameters are warranted with this combination.
Heparin: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. In clinical trials of cardiac stenting, patients were treated with heparin and ticlopidine concomitantly for 12 hours. The tolerance and long term safety of coadministered ticlopidine with these drugs has not been established. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Hydantoins: (Moderate) Ticlopidine is an inhibitor of the hepatic isoenzyme CYP2C19 and has been shown to reduce the clearance of phenytoin in patients previously on a stable phenytoin dosage regimen. Hydantoin dosage adjustments may be necessary in some patients who receive ticlopidine concurrently.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as platelet inhibitors; the risk of bleeding may be increased. If coadministration with platelet inhibitors is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibrutinib: (Moderate) The concomitant use of ibrutinib and antiplatelet agents such as ticlopidine may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood.
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Iloprost: (Moderate) When used concurrently with platelet inhibitors, inhaled iloprost may increase the risk of bleeding.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and ADP receptor antagonists due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of ADP receptor antagonists in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Intravenous Lipid Emulsions: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Levomilnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of levomilnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and ticlopidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticlopidine inhibits CYP1A2.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and ticlopidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticlopidine inhibits CYP1A2.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and ticlopidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticlopidine inhibits CYP1A2.
Lomustine, CCNU: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as lomustine.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with ticlopidine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and ticlopidine is a strong CYP2C19 inhibitor.
Mercaptopurine, 6-MP: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Methoxsalen: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs including increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants or antiplatelets including clopidogrel until data confirming the safety of these drug combinations are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving clopidogrel should be observed for increased bleeding.
Milnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of milnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
Mycophenolate: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Naproxen; Esomeprazole: (Minor) Ticlopidine may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as esomeprazole.
Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding.
Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle.
Olanzapine; Fluoxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., ticlopidine). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Omeprazole; Sodium Bicarbonate: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Paroxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Pentosan: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Pentostatin: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Pentoxifylline: (Moderate) A potential additive risk for bleeding exists if platelet inhibitors are given in combination with other agents that affect hemostasis such as pentoxifylline.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with ticlopidine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phenytoin: (Moderate) Ticlopidine is an inhibitor of the hepatic isoenzyme CYP2C19 and has been shown to reduce the clearance of phenytoin in patients previously on a stable phenytoin dosage regimen. Hydantoin dosage adjustments may be necessary in some patients who receive ticlopidine concurrently.
Photosensitizing agents (topical): (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Platelet Glycoprotein IIb/IIIa Inhibitors: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Pretomanid: (Major) Avoid coadministration of pretomanid with ticlopidine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Purine analogs: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and ticlopidine. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; ticlopidine is a weak CYP1A2 inhibitor. When administered with a strong CYP1A2 inhibitor, the AUC of rasagiline was increased by 83%.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ticlopidine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rivaroxaban: (Major) Avoid concurrent administration of platelet inhibitors such as clopidogrel with rivaroxaban unless the benefit outweighs the risk of increased bleeding. An increase in bleeding time to 45 minutes was observed in two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) and rivaroxaban (15 mg single dose) were coadministered in healthy subjects. In the first study, the increase in bleeding time to 45 minutes was observed in approximately 45% of patients. Approximately 30% of patients in the second study had the event. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. No change in the pharmacokinetic parameters of either drug were noted.
Selumetinib: (Moderate) Closely monitor for bleeding if coadministration of selumetinib and platelet inhibitors is necessary as concurrent use may increase the bleeding risk; adjust the platelet inhibitor dose as appropriate. Selumetinib contains vitamin E which can inhibit platelet aggregation.
Sertraline: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Sodium Bicarbonate: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with ticlopidine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2B6 substrate; ticlopidine is a potent inhibitor of CYP2B6.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with ticlopidine. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2B6 substrate; ticlopidine is a potent inhibitor of CYP2B6.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ticlopidine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19; ticlopidine is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Theophylline, Aminophylline: (Major) Aminophylline clearance may be significantly reduced when ticlopidine is administered concomitantly. Aminophylline serum concentrations should be monitored when ticlopidine is added or withdrawn. (Major) Coadministration of theophylline and ticlopidine can result in increased theophylline exposure and risk for toxicity. Theophylline half-life increased from 8.6 hours to 12.2 hours in healthy volunteers when ticlopidine was added. Monitor serum theophylline concentrations and signs of theophylline toxicity and efficiacy when ticlopidine is added to or withdrawn from a medication regimen containing theophylline.
Thioguanine, 6-TG: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Thrombolytic Agents: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving platelet inhibitors. In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including platelet inhibitors, that may have caused or contributed to these events.
Tirofiban: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
Tizanidine: (Major) Tizanidine is primarily metabolized by CYP1A2. If possible, avoid the concurrent use of tizanidine with other CYP1A2 inhibitors, such as ticlopidine, as concurrent use could lead to substantial increases in tizanidine blood concentrations. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Tofacitinib: (Moderate) A reduction in tofacitinib dose may be necessary if tofacitinib is coadministered with ticlopidine (a strong CYP2C19 inhibitor) and a medication that is a moderate CYP3A4 inhibitor. Tofacitinib exposure is increased when coadministered with both a strong CYP2C19 and a moderate CYP3A4 inhibitor. Review the patient's other medications for this potential drug interaction and the possible need for tofacitinib dose reduction. Tofacitinib is a CYP3A4 and CYP2C19 substrate. Coadministration of tofacitinib with both a strong CYP2C19 and a moderate CYP3A4 inhibitor increased tofacitinib exposure by 1.75-fold.
Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Treprostinil: (Moderate) Monitor patients for signs and symptoms of bleeding if treprostinil is administered with ticlopidine. Treprostinil inhibits platelet aggregation; ticlopidine is a platelet inhibitor. Coadministration increases the risk of bleeding.
Venlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with platelet inhibitors is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with salicylates or other platelet inhibitors and to promptly report any bleeding events to the practitioner. Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., aspirin, cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors).
Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine.
Vorinostat: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of ticlopidine and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Warfarin: (Moderate) Closely monitor patients for increased bleeding and monitor their INR if coadministration of warfarin with ticlopidine is necessary; concurrent use may increase the exposure of warfarin. Ticlopidine is a CYP1A2 inhibitor and the R-enantiomer of warfarin is a CYP1A2 substrate. Also, because ticlopidine inhibits platelet aggregation, additive risk for bleeding is possible when ticlopidine is given in combination with anticoagulants such as warfarin. It has been reported that the concomitant use of warfarin and ticlopidine may be associated with cholestatic hepatitis. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.

Ticlid/Ticlopidine/Ticlopidine Hydrochloride Oral Tab: 250mg

500 mg/day PO.

500 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mechanism of Action: Ticlopidine is a thienopyridine compound which acts to antagonize adenosine diphosphate (ADP). Ticlopidine interferes with the ADP-induced binding of fibrinogen to the platelet membrane at specific receptor sites. Platelet adhesion and platelet-platelet interactions are subsequently inhibited. Ticlopidine also affects blood viscosity and reduces fibrinogen concentrations, which is of benefit to patients with vascular disease. The inhibitory effects on platelet aggregation are irreversible; they begin within 24—48 hours and reach a maximum at 5—6 days of therapy. Antiplatelet activity persists for at least 72 hours after discontinuation of therapy. Platelet function returns to normal within 1—2 weeks as new platelets are generated.

Ticlopidine is administered orally. Steady-state concentrations are achieved in 14—21 days. Plasma protein binding is high (98%), mostly to serum albumin and lipoproteins. Alpha-1-acid glycoprotein binds <= 15% of the drug at therapeutic concentrations. 
 
Ticlopidine is extensively metabolized. Thirteen metabolites have been identified in rats and 4 in humans. The 2-keto metabolite is 5—10 times more potent than the parent compound. Plasma concentrations do not increase proportionally to the dose, which may be accounted for by saturation of biotransformation. 
 
Only trace amounts of intact ticlopidine have been detected in the urine. Renal excretion of metabolites accounts for 60% of elimination, while biliary circulation and unchanged drug will result in roughly 23% of a dose being excreted in the feces. The rate of normalization of platelet function is more a function of the accumulation of new (e.g., unaffected) platelets as opposed to the elimination half-life of the drug.
 
Affected cytochrome P450 isoenzymes and drug transporters:  CYP1A2, CYP2B6, CYP2C19
Ticlopidine is a potent inhibitor of CYP2C19 and CYP2B6 and a mild inhibitor of CYP1A2. By inhibiting these isoenzymes, ticlopidine theoretically could increase the plasma concentrations of drugs that are metabolized by CYP2C19, CYP2B6, or CYP1A2.

Ticlopidine is rapidly and well (>= 80%) absorbed. Bioavailability is enhanced about 20% when the drug is administered with food. Peak plasma concentrations are achieved in about 2 hours, but platelet-aggregation inhibition is not significant until after approximately 4 days of regular dosing.

According to the manufacturer, studies in rats have shown ticlopidine is excreted in the milk. It is not known whether ticlopidine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for drug reactions in nursing infants, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.