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Cardiology Case No 4.Clopidogrel And Aspirin.

Clopidogrel and Aspirin দুইটাই এন্টি প্ল্যাটিলেট, Ischemic heart disease e first line Drug Aspirin, তবে এইটা GIT upset করে অনেক বেশি, তাই পেশেন্ট এর ইকোনমিক কন্ডিশন ভালো থাকলে drug of choice হবে clopidogrel, আর পেশেন্ট এর এসিডিটি সমস্যা থাকলে Clopid দিয়েই শুরু করবে, এইটা রক্ত জমাট প্রিভেন্ট করে, Heart attack prevent করে।

একজন পেশেন্ট এর হার্ট অ্যাটাক হলে তাকে প্রথম এক বছর এর জন্য ডুয়েল এন্টি প্ল্যাটিলেট দেওয়া হবে,

তার মধ্যে ১ টা হবে Aspirin, আর অন্যটি হবে Prasugrel অথবা Ticagrelor.. এক বছর পর শুধু Aspirin অথবা clopid চলবে।

Prasugrel /Ticagrelor কিনতে না পারলে Aspirin + Clopid combination দিয়ে প্রথম বছর ডুয়েল এন্টি প্ল্যাটিলেট থেরাপি কন্টিনিউ করবে, এর পর যে কোনো একটা।

dose

Tablet 1.

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

1+0+0

Indications of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

Ecosprin is indicated in the following indications-

  • Prophylaxis against arterial occlusive events: Myocardial infarction, myocardial re-infarction, after bypass surgery, acute ischaemic stroke/TIA.
  • Mild to moderate pain: Headache, muscle pain, dysmenorrhoea and toothache etc.
  • Chronic disease accompanied by pain and inflammation: Osteoarthritis.
  • Antipyretic: Cold fever and influenzae.

Pharmacology of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

By decreasing platelet aggregation, Aspirin inhibits thrombus formation on the arterial side of the circulation, where thrombi are formed by platelet aggregation and anticoagulants have little effect. Aspirin is the analgesic of choice for headache, transient musculoskeletal pain and dysmenorrhoea. It has anti-inflammatory and antipyretic properties, which may be useful. Enteric-coated Aspirin reduces intestinal disturbance and gastrointestinal ulceration due to aspirin.

Dosage & Administration of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

Pain, inflammatory diseases and as antipyretic: Aspirin 300 mg 1-3 tablets 6 hourly with a maximum daily dose of 4 gm.

Suspected acute coronary syndrome: 150 mg-300 mg immediately unless there are clear contraindications.

After myocardial infarction: Aspirin 150 mg daily for 1 month. Long-term use of aspirin in a dose of 75 mg daily is recommended thereafter.

Acute ischaemic stroke/Transient ischaemic stroke (TIA): The starting dose is 150 mg-300 mg daily and Aspirin 75 mg daily thereafter.

Following bypass surgery: 75 mg-300 mg daily starting 6 hours post-procedure.

Interaction of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

Salicylates may enhance the effect of anticoagulants, oral hypoglycaemic agents, phenytoin and sodium valporate. They inhibit the uricosuric effect of probenecid and may increase the toxicity of sulphonamides. They may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.

Contraindications

Aspirin is contraindicated to the children (Reye’s syndrome) less than 12 years, in breast-feeding and active peptic ulcer. It is also contraindicated in bleeding due to haemophilia, intracranial haemorrhage and other ulceration.

Side Effects of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

Side effects for the usual dosage of Ecosprin are mild including nausea, dyspepsia, gastrointestinal ulceration and bronchospasm etc.

Pregnancy & Lactation of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

It is especially important not to use aspirin during the last 3 months of pregnancy unless specifically directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery. Aspirin penetrates into breast milk. So, it should be administered with caution to lactating mothers.

Precautions & Warnings

It should be administered cautiously in asthma, uncontrolled blood pressure, and pregnant women. It should be administered with caution to patients with a nasal polyp and nasal allergy.

Overdose Effects

Overdosage produces dizziness, tinnitus, sweating, nausea and vomiting, confusion and hyperventilation. Gross overdosage may lead to CNS depression with coma, cardiovascular collapse and respiratory depression. If the overdosage is suspected, the patient should be kept under observation for at least 24 hours, as symptoms and salicylate blood levels may not become apparent for several hours. Treatment of overdosage consists of gastric lavage and forced alkaline diuresis. Haemodialysis may be necessary in severe cases.

Therapeutic Class of Tablet:-

Ecospirin 75 mg (AS A Aspirin AS A Anti-platelet drugs).

Anti-platelet drugs

Tablet 2. Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

1+0+1 (1 year)

Indications of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Ticaflow, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndromes (ACS) or a history of myocardial infarction (MI) and a high risk of developing an atherothrombotic event.

Pharmacology of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Ticagrelor is a P2Y12 receptor antagonist. The P2Y12 receptor couples with Gαi2 and other Gi proteins which inhibit adenylyl cyclase. Gi mediated signalling also activates PI3K, Akt, Rap1b, and potassium channels. The downstream effects of these activities mediate hemostasis and lead to platelet aggregation. Antagonism of the P2Y12 receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke.

Dosage & Administration of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Patients taking Ticagrelor should also take a daily low maintenance dose of acetylsalicylic acid (ASA) 75-150 mg unless specifically contraindicated.

Acute coronary syndromes: Ticagrelor treatment should be initiated with a single 180 mg loading dose (two tablets of 90 mg) and then continued at 90 mg twice daily. Treatment with Ticagrelor twice daily is recommended for 12 months in ACS patients unless discontinuation is clinically indicated.

History of myocardial infarction: Ticagrelor 60 mg twice daily is the recommended dose when an extended treatment is required for patients with a history of MI of at least one year and a high risk of an atherothrombotic event. Treatment may be started without interruption as continuation therapy after the initial one-year treatment with ticagrelor or another adenosine diphosphate (ADP) receptor inhibitor therapy in ACS patients with a high risk of an atherothrombotic event. Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment. There are limited data on the efficacy and safety of ticagrelor beyond 3 years of extended treatment.

Switch therapy: If a switch is needed, the first dose of ticagrelor should be administered 24 hours following the last dose of the other antiplatelet medication.

Missed dose: A patient who misses a dose of ticagrelor should take only one tablet (their next dose) at its scheduled time.

Elderly: No dose adjustment is required in the elderly.

Renal impairment: No dose adjustment is necessary for patients with renal impairment. No information is available concerning the treatment of patients on renal dialysis and therefore ticagrelor is not recommended in these patients.

Hepatic impairment: Ticagrelor has not been studied in patients with severe hepatic impairment and its use in these patients is therefore contraindicated. Only limited information is available in patients with moderate hepatic impairment. Dose adjustment is not recommended, but ticagrelor should be used with caution. No dose adjustment is necessary for patients with mild hepatic impairment.

Pediatric population: The safety and efficacy of ticagrelor in hildren below the age of 18 years have not been established. No data are available. Ticagrelor can be administered with or without food. Contra-indications, warnings etc.

Interaction of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Effects of medicinal and other products on Ticaflow;

CYP3A4 inhibitors: Concomitant use of strong CYP3A4 clarithromycin, nefazodone, ritonavir, and atazanavir) inhibitors with Ticaflow is contraindicated.

CYP3A inducers: Co-administration of Ticaflow with potent CYP3A inducers (rifampicin)may decrease exposure and efficacy of Ticaflow, therefore, their concomitant use with Ticaflow is discouraged.

Cyclosporine (P-gp and CYP3A inhibitor): No data are available on concomitant use of Ticaflow with other active substances that also are potent P-gp inhibitors and moderate CYP3A4 inhibitors (e.g. verapamil, quinidine) that also may increase Ticaflow exposure. If the association cannot be avoided, their concomitant use should be made with caution.

Effects of Ticaflow on other medicinal products: Medicinal products metabolised by CYP3A4: The concomitant use of Ticaflow with doses of simvastatin or lovastatin greater than 40 mg is not recommended. Atorvastatin: Co-administration of atorvastatin and Ticaflow increased atorvastatin acid Cmax by 23% and AUC by 36%. Similar increases in AUC and Cmax were observed for all atorvastatin acid metabolites. These increases are not considered clinically significant. Ticaflow is a mild CYP3A4 inhibitor. Co-administration of Ticaflow and CYP3A4 substrates with narrow therapeutic indices (i.e. cisapride or ergot alkaloids) is not recommended, as Ticaflow may increase the exposure to this medicinal products.

P-gp substrates (including digoxin, cyclosporine): Appropriate clinical and/or laboratory monitoring is recommended when giving narrow therapeutic index P-gp dependent medicinal products like digoxin concomitantly with Ticaflow.

Medicinal products metabolised by CYP2C9: Co-administration of Ticaflow with tolbutamide resulted in no change in the plasma levels of either medicinal product, which suggests that Ticaflow is not a CYP2C9 inhibitor and unlikely to alter the CYP2C9 mediated metabolism of medicinal products like warfarin and tolbutamide.

Oral contraceptives: No clinically relevant effect on oral contraceptive efficacy is expected when levonorgestrel and ethinyl estradiol is co-administered with Ticaflow.

Medicinal products known to induce bradycardia: No evidence of clinically significant adverse reactions were observed in the PLATO trial after concomitant administration with one or more medicinal products known to induce bradycardia (e.g. 96% beta blockers, 33% calcium channel blockers diltiazem and verapamil, and 4% digoxin).

Other concomitant therapy: No evidence of clinically significant adverse interactions with these medicinal products (acetylsalicylic acid, proton pump inhibitors, statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers) was observed. Due to potential pharmacodynamic interactions, caution should be exercised with the concomitant administration of Ticaflow with medicinal products (heparin, enoxaparin or desmopressin) known to alter haemostasis. Due to reports of cutaneous bleeding abnormalities with SSRIs (e.g. paroxetine, sertraline and citalopram), caution is advised when administering SSRIs with Ticaflow as this may increase the risk of bleeding.

Contraindications of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Hypersensitivity to the active substance or to any of the excipients, active pathological bleeding, history of intracranial haemorrhage, severe hepatic impairment.

Side Effects of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Very Common: Blood disorder bleedings, Hyperuricaemia, Dyspnoea. Common: Gout/Gouty Arthritis, Dizziness, Syncope, Headache, Vertigo, Hypotension, Respiratory system bleedings, Gastrointestinal haemorrhage, Diarrhoea, Nausea, Dyspepsia, Constipation, Subcutaneous or dermal bleeding, Rash, Pruritus, Urinary tract bleeding, Blood creatinine increased, Postprocedural haemorrhage, Traumatic bleedings. Uncommon: Tumour bleedings, Hypersensitivity including angioedema, Confusion, Intracranial haemorrhage, Eye haemorrhage, Ear haemorrhage, Retroperitoneal haemorrhage, Muscular bleedings.

Pregnancy & Lactation of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Ticagrelor is not recommended during pregnancy. Available pharmacodynamic/toxicological data in animals have shown excretion of ticagrelor and its active metabolites in milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ticagrelor therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Precautions & Warnings of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Bleeding risk: The use of Ticaflow in patients at known increased risk for bleeding should be balanced against the benefit in terms of prevention of atherothrombotic events. If clinically indicated, Ticaflow should be used with caution in the following patient groups; Patients with a propensity to bleed (e.g. due to recent trauma, recent surgery, coagulation disorders, active or recent gastrointestinal bleeding). Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and/or recombinant factor VIIa therapy may increase haemostasis. Ticaflow may be resumed after the cause of bleeding has been identified and controlled.

Surgery: Patients should be advised to inform  physicians and dentists that they are taking Ticaflow before any surgery is scheduled and before any new medicinal product is taken. If a patient is to undergo elective surgery and the antiplatelet effect is not desired, Ticaflow should be discontinued 5 days prior to surgery.

Patients with prior ischaemic stroke: ACS patients with prior ischaemic stroke can be treated with Ticaflow for up to 12 months. Patients at risk for bradycardic events: Due to the limited clinical experience, Ticaflow should be used with caution in these patients.

Dyspnoea: Patients with asthma/chronic obstructive pulmonary disease (COPD) may have an increased absolute risk of experiencing dyspnoea with Ticaflow. Ticaflow should be used with caution in patients with a history of asthma and/or COPD. Creatinine elevations: Creatinine levels may increase during treatment with Ticaflow. In patients with ACS, it is recommended that renal function is also checked one month after initiating the treatment with Ticaflow, paying special attention to patients ≥75 years, patients with moderate/severe renal impairment and those receiving concomitant treatment with an angiotensin receptor blocker (ARB). Uric acid increase: Hyperuricaemia may occur during treatment with Ticaflow. Caution is advised in patients with a history of hyperuricaemia or gouty arthritis. Other: Based on a relationship observed in PLATO between maintenance dose of acetylsalicylic acid (ASA) and relative efficacy of Ticaflow compared to clopidogrel, co-administration of Ticaflow and high maintenance dose of acetylsalicylic acid (ASA) (>300 mg) is not recommended.

Premature discontinuation: Premature discontinuation with any antiplatelet therapy, including Ticaflow, could result in an increased risk of cardiovascular (CV) death or MI due to the patient’s underlying disease. Therefore, premature discontinuation of treatment should be avoided.

Overdose Effects of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Ticaflow is well tolerated in single doses up to 900 mg. Gastrointestinal toxicity was dose-limiting in a single ascending dose study. Other clinically meaningful adverse reactions which may occur with overdose include dyspnoea and ventricular pauses.

Therapeutic Class of Tablet :- Ticaflow 90 mg AS A (Ticagrelor) AS A (Anti-platelet drugs).

 

Anti-platelet drugs

Ticagrelor এর দাম অনেক বেশি, (দৈনিক ১৫০ টাকা) তাই কেউ এইটা কিনতে না পারলে তাকে Prasugrel দিবে। (দৈনিক ২০ টাকা লাগবে)

Tablet 3.- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

0+0+1 (এক বছর)

Indications of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Prasurel is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows:

  • Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI).
  • Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.

Pharmacology of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel.

Dosage & Administration of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Adults: Prasugrel should be initiated with a single 60mg loading dose and then continued at 10 mg once a day. Patients taking Prasugrel should also take ASA daily (75 mg to 325 mg). In patients with acute coronary syndrome (ACS) who are managed with PCI, premature discontinuation of any antiplatelet agent, including Prasugrel, could result in an increased risk of thrombosis, myocardial infarction or death due to the patient’s underlying disease. A treatment of up to 12 months is recommended, unless the discontinuation of Prasugrel is clinically indicated.

Patients ≥75 years old: The use of Prasugrel in patients ≥75 years of age is generally not recommended. If, after a careful individual benefit/risk evaluation by the prescribing physician, treatment is deemed necessary in the patients age group ≥75 years, then following a 60mg loading dose a reduced maintenance dose of 5 mg should be prescribed. Patients ≥75 years of age have greater sensitivity to bleeding and higher exposure to the active metabolite of prasugrel.

Patients weighing <60 kg: Prasugrel should be given as a single 60mg loading dose and then continued at a 5mg once-daily dose. The 10mg maintenance dose is not recommended. This is due to an increase inexposure to the active metabolite of prasugrel, and an increased risk of bleeding in patients with body weight <60 kg when given a 10mg once-daily dose, compared with patients <60 kg.

Renal impairment: No dose adjustment is necessary for patients with renal impairment, including patients with end-stage renal disease.

Hepatic impairment: No dose adjustment is necessary in subjects with mild to moderate hepatic impairment (Child-Pugh class A and B). There is limited therapeutic experience in patients with mild and moderate hepatic dysfunction.

Children and adolescents: Prasugrel is not recommended for use in children below age 18 due to a lack of data on safety and efficacy.

Interaction of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Warfarin: Coadministration of Prasurel and warfarin increases the risk of bleeding.

Non-Steroidal Anti-Inflammatory Drugs: Coadministration of Prasurel and NSAIDs (used chronically) may increase the risk of bleeding.

Other Concomitant Medications: Prasurel can be administered with drugs that are inducers or inhibitors of cytochrome P450 enzymes. Prasurel can be administered with aspirin (75mg to 325mg per day), heparin, GPIIb/IIIa inhibitors, statins, digoxin, and drugs that elevate gastric pH, including proton pump inhibitors and H2.

Contraindications of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Prasugrel is contraindicated in patients with Hypersensitivity to the active substance or to any of the excipients, active pathological bleeding, history of stroke or transient ischaemic attack (TIA), severe hepatic impairment (Child-Pugh class C)

Side Effects of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Common: Anaemia, Haematoma, Epistaxis, Gastrointestinal haemorrhage, Rash, Ecchymosis, Haematuria, Vessel puncture site haematoma, Puncture site haemorrhage, Contusion. 

Uncommon: Hypersensitivity including angioedema, Eye haemorrhage, Haemoptysis, Retroperitoneal haemorrhage, Rectal haemorrhage, Haematochezia, Gingival bleeding, Post-procedural haemorrhage.

Rare: Thrombocytopaenia, Subcutaneous haematoma.

Pregnancy & Lactation of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

There are no adequate and well-controlled studies of Prasugrel use in pregnant women. Reproductive and developmental toxicology studies in rats and rabbits at doses of up to 30 times the recommended therapeutic exposures in humans revealed no evidence of fetal harm; however, animal studies are not always predictive of a human response.

It is not known whether Prasugrel is excreted in human milk. Because many drugs are excreted in human milk, Prasugrel should be used during nursing only if the potential benefit to the mother justifies the potential risk to the nursing infant.

Precautions & Warnings of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Bleeding risk: In the phase 3 clinical trial, key exclusion criteria included an increased risk of bleeding; anaemia; thrombocytopaenia; a history of pathological intracranial findings. Patients with acute coronary syndromes undergoing PCI treated with Prasurel and ASA showed an increased risk of major and minor bleeding according to the TIMI classification system. Therefore, the use of Prasurel in patients at increased risk of bleeding should only be considered when the benefits in terms of prevention of ischaemic events are deemed to outweigh the risk of serious bleedings. This concern applies especially to patients:

  • Age ≥75 years.
  • With a propensity to bleed (e.g., due to recent trauma, recent  surgery, recent or recurrent gastrointestinal bleeding, or active  peptic ulcer disease).
  • With body weight <60 kg. In these patients the 10mg  maintenance dose is not recommended. A 5mg maintenance  dose should be used.
  • With concomitant administration of medicinal products that  may increase the risk of bleeding, including oral anticoagulants,  clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), and  fibrinolytics.

Surgery: Patients should be advised to inform physicians and dentists that they are taking prasugrel before any surgery is scheduled, and before any new medicinal product is taken. If a patient is to undergo elective surgery, and an antiplatelet effect is not desired, Prasurel should be discontinued at least 7 days prior to surgery. Increased frequency (3-fold) and severity of bleeding may occur in patients undergoing CABG surgery within 7 days of discontinuation of prasugrel . The benefits and risks of prasugrel should be carefully considered in patients in whom the coronary anatomy has not been defined, and urgent CABG is a possibility.

Overdose Effects of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Overdose of Prasurel may lead to prolonged bleeding time and subsequent bleeding complications. No data are available on the reversal of the pharmacological effect of prasugrel; however, if prompt correction of prolonged bleeding time is required, platelet transfusion and/or other blood products may be considered. Pharmaceutical precautions Store in a cool and dry place, protected from light.

Therapeutic Class of Tablet:- Prasurel 10 mg AS A (Prasugrel Hydrochloride ) (AS A Anti-platelet drugs ).

Anti-platelet drugs

General Queries:

1.Aspirin সব সময়েই দেখেছি দুপুরে দিতে। এর কি কোন কারণ আছে? নাকি যেকোন সময়ে দেওয়া যায়?

Answer is:Any time can be used

2.For preventive purpose

Start as 1st line with aspirin

if pud persistes or aspirin intolerance then go for clopid

if cardiac events occurred already then use clopid-as combination

Erkom ta kothai jani porsilam…reference mone nai.

Answer is:Nice guideline.

Ref: NICE Guideline Raiyyan Tahsan Date:-28-01-2025 Tuesday Time:-10-57-55 AM

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