Ticlopidine (Ticlid) is a platelet aggregation inhibitor that reduces the risk of thrombotic stroke in patients who have had a stroke or stroke precursors. Ticlopidine should be used in patients who are intolerant to aspirin, who have failed aspirin therapy, or who are not eligible to receive other antiplatelet therapy.
Ticlopidine (Ticlid) dose in Adults
Note: Ticlopidine has been discontinued in the US.
Dose in the prevention of Stroke:
- Oral: 250 mg twice daily given
Ticlopidine (Ticlid) dose in Childrens
Not recommended for use in children.
Pregnancy Risk Factor B
- In animal reproduction studies, teratogenic effects were not studied.
Ticlopidine use during breastfeeding:
- It is unknown if ticlopidine can be excreted in breastmilk.
- Nursing infants could experience serious adverse reactions. It is important to decide whether to stop breastfeeding or discontinue using the drug.
Ticlopidine (Ticlid) dose in kidney disease:
- There is no dosage adjustment given in the manufacturer's labeling.
- Bleeding time may be prolonged in patients with moderate renal impairment
Hemodialysis:
- Not dialyzable
Ticlopidine (Ticlid) dose in liver disease:
- There is no dosage adjustments given in the manufacturer's labeling.
- Use cautiously.
- Use is contraindicated in severe hepatic impairment.
Ticlopidine use is associated with bleeding. Hemorrhage may occur at virtually any site. The risk is dependent on multiple variables, including the use of multiple agents that alter hemostasis and patient susceptibility.
Common Side Effects of Ticlopidine Include:
-
Endocrine & metabolic:
- Hyperlipidemia
- Increased serum triglycerides
-
Gastrointestinal:
- Diarrhea
Less Common Side Effects Include:
-
Central Nervous System:
- Dizziness
-
Dermatologic:
- Skin Rash
- Pruritus
-
Gastrointestinal:
- Dyspepsia
- Nausea
- Gastrointestinal Pain
- Flatulence
- Vomiting
- Anorexia
-
Hematologic & Oncologic:
- Neutropenia
- Purpura
-
Hepatic:
- Increased Serum Alkaline Phosphatase
- Abnormal Hepatic Function Tests
Contraindication to Ticlopidine Include:
- Hypersensitivity to ticlopidine and any component of the formulation
- Active pathological bleeding, such as intracranial hemorhage or peptic ulcer bleeding, can occur.
- severe liver derangement
- Blood disorders such as neutropenia, hemorhagic fever, thrombocytopenia or anemia may be present.
- Hemostatic disorders
Warnings and precautions
-
Hematologic toxicities: [US Boxed Warning]
- It is possible to have life-threatening hematologic reactions. These reactions include neutropenia and agranulocytosis.
- Routine monitoring is often necessary.
- You should look out for symptoms such as neutropenia, including WBC count.
- If the absolute neutrophil count drops below 1,200/mm, or if there are laboratory signs of TTP and aplastic anemia, stop immediately.
-
Hypersensitivity to Thienopyridine:
- Cross-reactivity between the thienopyridines (prasugrel and Clopidogrel) is possible due to their structural similarities.
- Patients with a history of thienopyridine hypersensitivity should be cautious and avoid.
- Patients with hypersensitivity to Tilopidine should not be given ticlopidine.
-
Bleeding disorders:
- Patients with bleeding disorders or platelet disorders should be supervised.
-
Hepatic impairment
- Patients with mild-to moderate hepatic impairment should be cautious.
- With severe hepatic impairment, use is not recommended.
-
Renal impairment
- Patients with severe to moderate renal impairment should be cautious (experience is limited).
- The bleeding time can be prolonged and there is a higher risk of hemorhagic adverse events (eg neutropenia).
Ticlopidine (United States: Not available): Drug Interaction
|
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.) |
May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. |
|
Anticoagulants |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. |
|
ARIPiprazole |
CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
BuPROPion |
CYP2B6 Inhibitors (Weak) may increase the serum concentration of BuPROPion. |
|
Cephalothin |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. |
|
CloZAPine |
CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Collagenase (Systemic) |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Dasatinib |
May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Deoxycholic Acid |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Fat Emulsion (Fish Oil Based) |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. |
|
FentaNYL |
May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). FentaNYL may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). |
|
Fosphenytoin |
Ticlopidine may increase the serum concentration of Fosphenytoin. |
|
Glucosamine |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Ibritumomab Tiuxetan |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. |
|
Ibrutinib |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. |
|
Inotersen |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Limaprost |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Multivitamins/Fluoride (with ADE) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Multivitamins/Minerals (with ADEK, Folate, Iron) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Multivitamins/Minerals (with AE, No Iron) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Obinutuzumab |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. |
|
Omega-3 Fatty Acids |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Pentosan Polysulfate Sodium |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. |
|
Pentoxifylline |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Perhexiline |
CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. |
|
Phenytoin |
Ticlopidine may increase the serum concentration of Phenytoin. |
|
Prostacyclin Analogues |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Salicylates |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Sibutramine |
CYP2B6 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP2B6 Inhibitors (Weak) may increase the serum concentration of Sibutramine. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Theophylline Derivatives |
Ticlopidine may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. |
|
Thrombolytic Agents |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. |
|
Tipranavir |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Vitamin E (Systemic) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Apixaban |
Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. |
|
Bemiparin |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. |
|
Cilostazol |
CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. |
|
CYP3A4 Inducers (Strong) |
May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Dabigatran Etexilate |
Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Antiplatelet Agents (P2Y12 Inhibitors) may increase the serum concentration of Dabigatran Etexilate. Specifically, clopidogrel may increase dabigatran serum concentrations. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Edoxaban |
Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. |
|
Enoxaparin |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Heparin |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. |
|
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry) |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Morphine (Systemic) |
May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Morphine (Systemic) may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Management: Consider alternative anti-ischemic/analgesic therapies (eg, beta-blockers, nitroglycerin) in patients with acute coronary syndromes treated with a P2Y12 inhibitor when possible. The risks associated with other opioids are unknown. |
|
Rivaroxaban |
Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. |
|
St John's Wort |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
TiZANidine |
CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. |
|
Urokinase |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. |
Monitor:
- Signs of bleeding
- CBC with differential at baseline prior to treatment initiation and then weekly for the first 3 months of therapy
- more frequent monitoring is advised for patients whose absolute neutrophil counts have been consistently declining or are 30% less than baseline values.
- Liver function tests (alkaline phosphatase and transaminases) should be done in the first 4 months of therapy if liver dysfunction is suspected.
How to administer Ticlopidine (Ticlid)?
Administer with food.
Mechanism of action:
- Ticlopidine requires in vivo biotransformation into an unidentified active substance.
- The active metabolite blocks irreversibly the P2Y12 part of ADP receptors.
- This prevents activation by the GPIIb/IIIa complex and reduces platelet aggregation.
- For the rest of their lives, platelets that have been blocked by ticlopidine will be affected.
Onset of action:
- almost 6 hours
Peak effect:
- 3-5 days
- serum levels do not correlate with clinical antiplatelet activity
Absorption:
- Well absorbed
Protein binding:
- Parent drug: 98%;
- <15% is bound to alpha -acid glycoprotein
Metabolism:
- Extensively hepatic; has at least 1 active metabolite
Half-life elimination:
- 13 hours
Time to peak, serum:
- ~2 hours
Excretion:
- By Urine (60%) & feces (23%)
International Brands of Ticlopidine:
- Apo-Ticlopidine
- Teva-Ticlopidine
- Anagregal
- Antigreg
- Aplaket
- Ban Su
- Cartrilet
- Cenpidine
- Clid
- Declot
- Desitic
- Ebrilon
- Gotik
- Ipaton
- Licodin
- Nichistate
- Panaldine
- Piclodin
- Plaquetil
- Prevoc
- Strokan FC
- Tagren
- Ticard
- Ticlid
- Ticlo
- Ticlod
- Ticlodin
- Ticlodix
- Ticlodone
- Ticlop
- Ticlopid
- Ticlopide
- Ticlopine
- Ticolid
- Ticopar
- Ticuring
- Tikleen
- Tiklid
- Tiklyd
- Tikpid
- Tiodin
- Tipidin
- Tipidine
- Tyklid
Ticlopidine (Ticlid) Brands in Pakistan:
Ticlopidine (HCl) [Tabs 250 mg] |
|
| Clopidine | Hoffman Health Pakistan Ltd. |
| Tekopin | Bayer Health Care |
| Teolid | Highnoon Laboratories Ltd. |
| Ticlopoli | Scharper Pharmaceuticals (Pvt) Ltd. |
| Ziclodin | Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
