Interacting drugs- Summary-

Antacids +  Ticlopodine       18% decrease in plasma levels

Cimetidine  + Ticlopodine        cimetidine admin reduced clearance of ticlopodine  by 50%

Ticlopodine  + Aspirin                  Ticlopodine potentiate action of aspirn

Ticlopodine  + Digoxin                 Digoxin levels may be decreased

Ticlopodine  +Theophylline         Theophylline elimination half-life increased
            
 

Reduce risk of thrombotic stroke

GI- ticlopodine has been associated with a variety of GI complaints. They usually occur within 3 months of initiation of therapy and typically are resolved within 1 to 2 weeks of without discontinuation of therapy.

Hemorrhage- Ticlopdine has been associated with a number of bleeding complicattions such as ecchymosis,epistaxis, hematuria, conjuntival hemorrhage, GI bleeding, and perioperative bleeding.

Rash- macropapular or urticarial rash (often with pruritus) .Rash usally occurs within 3 months of initiation of therapy with a mean onset time of 11 days. If the dug is discontinued recovery occurs within several days.

Miscellaneous- GI fullness, urticaria, headache, asthenia, pain, epistaxis, tinnitus

. Lab test abnormalities- elevations of alkaline phosphatase and transaminase generally within 1 to 4 months of therapy initiation.

Adverse reactions- %

Diarrhea 12%  Nausea 7% Dyspepsia 7 Rash 5%  GI pain 3% 

Neutropenia 2 %  Purpura 2% 

Vomiting 2%  Flatulance 2%

Pruritis 1% Dizziness 1%  Anorexia 1%

Pre existing defect in blood coagulation(haemophilia)

,platelet function(thrombocytopenia),vessel wall defect with prolonged bleeding time(von Wilferbrands disease) pre-existing disease where bleeding from local lesions is common(peptic ulceration,epistaxis,menorrhagia),

H/O neutropenia, agranulocytosis,leucopenia, thrombocyopenia, acute phase of haemorrhagic cerebrovascular accident,allergyto ticlopidine lactation.

Special precaution:

Pregnancy,neonates and children.

Increased bleeding time- use with caution in patients who may be at risk of increased bleeding from trauma, surgery, or pathological conditions.

GI bleeding- Ticlopdine prolongs template bleeding time. Use withcaution innpatients whohave lesions with apropensity to bleed (such as ulcers).

Warnings-

Thrombocytopenia- rarely thrombocytopenia may occur inisolatin or together with neutropenia. If clinical evaluaton and repeat testing confirm the presence of ninithrombocytopenia ,discontinue the drug.

Cholesterol elevation- ticlopodine therapy causes increased serum cholesterol and triglycerids

Hematological effects- rare cases of pancytopenia and thrombotic thrombocytopenia purpura , some of which fatal have occured.

Anticoagulant drugs- if a patient is switched from an anticoagulant or fibrolytic drug to ticlopodine discontinue the former prior to ticlopodine administration.

Renal function impairment- for renally impaired patients it may be necessary to reduce ticlopodine dosage or discontinue it altogether, if hemorrhagic or hematopoietic problems are encountered

Hepatic function impairment- in patients with severe hepatic disease who may have bleeding diatheses, the use of ticlopodine is not recommended.

Elderly- clearance of ticlopodine is somewhat lower in elderly patients and trough levels are increased.

Pregnancy- use during pregnancy only if clearly needed.

Lactation- because of the potential for serious adverse reactions in nursing infants from ticlopodine decide whether to discontinue nursing or discontinue the drug taking into consideration the importance of the drug to the mother.

Children- safety and efficacy in patients < 18 years of age have not been established.

Date of Approval        1993

Indications:

reduce risk of thrombotic stroke.

Dosage:

250 mg twice daily with food.

Overdosage-

One case of deliberate overdosage has been reported. Only abnormalities reported were increased bleeding time and increased ALT. No special therapy was instituted and the patient recovered without sequelae.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible unless the dose is less than 4 hours

. 2. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

EVIDENCE BASED MEDICINE (MIMS April 2003)

Stroke prevention Comparative effectiveness of various interventions

PRIOR TO STROKE OR TRANSIENT ISCHAEMIC ACCIDENT (TIA)

Beneficial

1. Antiplatelet treatment

2. Cholestrerol reduction (for those patients who also have coronary heart disease)

3. Carotid endarterectomy (in patients with severe symptomatic carotid artery stenosis)

Unknown effectiveness

1. Cholesterol reduction (for patients without CHD)

2. Blood pressure reduction

3. Carotid endarterectomy (in patients with severe symptomatic carotid artery stenosis)

4. Catotid angioplasty

Likely to ineffective or even harmful

1. Oral anticoagulation

ATRIAL FIBRILLATION AND A PRIOR STROKE OR TIA

Beneficial

1. Oral anticoagulation

2. Aspirin for patients with contraindications to an anticoagulant

ATRIAL FIBRILLATION BUT NO OTHER MAJOR RISK FACTORS FOR STROKE

Likely to be beneficial

1. Oral anticoagulation

2. Aspirin for patients with contraindications to an anticoagulant

KEY POINTS

In patients with a prior stroke or TIA

1. Insufficient evidence to support routine blood presure reduction

2. Statins may prevent stroke in those with a history of CHD but evidence inconclusive in those with no history of CHD.

3. Routine use of prolonged anti-platelet treatment beneficial ( if no contraindication)

4. Aspirin 75mg daily as effective as higher doses. No evidence that any other antiplatelet regimen is definitely superior in the prevention of vascular events. Clopidogrel or the combination of asprin and dipyridamole are safe and effective (but more costly) alternatives to aspirin

5. No evidence of benefit from anti-coagulation in patients in sinus rhythm, but an increased risk of serious bleeding

6. Carotid endarterectomy reduces risk of major stroke in patients with severe carotid stenosis provided the risks of imaging and surgery are small.

7. Percutaneous transluminal angioplastys role has not been evaluated adequately In patients with atrial fibrillation and a pror stroke or TIA

1. Anticoagulants reduce risk of stroke, provided there is low risk of bleeding and careful monitoring

2. Aspirin reduces risk of stroke but less effectively than anticoagulants. These findings support the use of aspirin among patients with atrial fibrillation and contra-indication to anticoagulants In patients with atrial fibrillation but neither major risk factors for stroke

1. Anticoagulants are of net benefit, if low risk of bleeding and careful monitoring

2. Aspirin is a reasonable alternative in patients with contra-indications to anticoagulants.

1.A decrease in the number of white cells(neutropenia) can occur,especially during the first 3 monts of treatment. If neutropenia is severe,it could result in an increased risk of infection.

2.Obtain the scheduled blood tests to detect neutropenia.

3.It may take longer than usual to stop bleeding when taking ticlopidine. Report unsual bleeding to the doctor.

4.Take ticlopidine with food or just after eating in order to minimise GI discomfort.

5. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to toclopidine. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

6.Pregnancy- studies have not been done on humans. This medicine did not cause birth defects in animal studies.

7.Breast feeding- not known wheteher ticlopodine passes into the breast milk

. 8.Children- no specific information comparing use of ticlopodine in children with use in other age groups.

9. Elderly- not shown tomcause different side effects or problems in older people than it does in younger groups.

10. Other medicines - Tell your doctor if you taking Anticoagulants or Carbenicillin or Dipyridamole or Divalproex or Heparin or Inflammation or pain medicine or Pentoxyphylline or Plicamycin or Sulfinpyrazone or Ticarcillin or Valproic acid - chance of serious effects may be increased

11. Other medical problems - Blood clotting problems or Liver disease or Stomach ulcers - chance of serious bleeding may be increased Blood disease - chance of serious side effects may be increased

  11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Date expired medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Increased bioavailabilty if given after meals.

Pregnancy:

Use during pregnancy only if clearly needed.

Lactation:

Excercise caution and decide whether to discontinue nursing or discontinue the drug depending the importance to the mother

Children-

Safety and efficacy in patients < 18 years of age have not been established.