Clopidogrel, History, Action, best Uses, Uses in Urdu, Benefits, Side effects, & Top10 brands

Introduction

Clopidogrel, also known as Plavix, is a medication used to prevent blood clots from forming and to treat conditions related to blood clotting. It belongs to a class of drugs called platelet inhibitors, which block blood clot formation. It is commonly used to treat acute coronary syndrome, peripheral artery disease, and cerebrovascular disease.

Clopidogrel is an important medication in the field of cardiology and has saved countless lives by reducing the risk of cardiovascular events.

History of Clopidogrel

Clopidogrel, a platelet inhibitor, has a fascinating history that spans over three decades.

Early Development (1980s)

• Sanofi, a French pharmaceutical company, began researching a new class of antiplatelet agents.
• Chemists at Sanofi synthesized Clopidogrel in 1982, and it was patented the same year.

Preclinical Studies (1980s-1990s)

• Researchers conducted extensive preclinical studies to evaluate Clopidogrel’s safety and efficacy.
• These studies demonstrated its potential in preventing platelet aggregation and thrombosis.

Clinical Trials (1990s)

• The first clinical trials were conducted in the late 1990s, focusing on acute coronary syndrome.
• The CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) trial, published in 1996, showed this medicine superiority over aspirin in reducing cardiovascular events.

FDA Approval and Marketing (1997-1998)

• On November 17, 1997, the US FDA approved Clopidogrel for treating acute coronary syndrome.
• Sanofi and Bristol-Myers Squibb jointly marketed Plavix (Clopidogrel) in the United States, launching it in 1998.

Expanded Indications and Generics (2000s-2010s)

• Clinical trials expanded Clopidogrel’s indications to include peripheral artery disease and cerebrovascular disease.
• Generic versions of Clopidogrel became available in the United States in 2012, increasing accessibility worldwide.

Ongoing Research and Legacy (Present Day)

• Researchers continue to explore Clopidogrel’s potential in new indications, such as atrial fibrillation and coronary artery disease.
• It remains a widely used and essential medication in cardiology, with millions of patients benefiting from its antiplatelet effects.

Clopidogrel mechanism of action

Clopidogrel, a thienopyridine-class platelet inhibitor, selectively blocks the P2Y12 receptor, a key player in platelet activation and aggregation. Here’s a detailed explanation of its mechanism of action:

• Absorption and Metabolism: Clopidogrel is absorbed from the gut and metabolized in the liver to its active metabolite, clopidogrel-active-metabolite (CAM).
• Binding to P2Y12 Receptor: CAM binds reversibly to the P2Y12 receptor on the platelet surface, blocking the binding of adenosine diphosphate (ADP).
• Inhibition of ADP-Mediated Signaling: By blocking ADP binding, it inhibits the activation of the G protein-coupled signaling cascade, which normally leads to platelet aggregation.
• Inhibition of Platelet Aggregation: The inhibition of ADP-mediated signaling reduces platelet aggregation and the formation of blood clots.
• Inhibition of Glycoprotein IIb/IIIa Activation: It also inhibits the activation of the glycoprotein IIb/IIIa complex, a key receptor involved in platelet aggregation.
• Antiplatelet Effect: The combined effects of Clopidogrel lead to a reduction in platelet aggregation, resulting in a decreased risk of cardiovascular events.

Clopidogrel uses

Doctors prescribe clopidogrel for various heart conditions, including, Heart attack, Angina, Cardiac stent, and others which are described below:

1. Prevention of Heart Attacks: Clopidogrel is prescribed to reduce the risk of heart attacks in individuals with a history of recent heart attack or unstable angina (a type of chest pain).
2. Prevention of Strokes: It helps prevent strokes in people with a history of recent stroke or transient ischemic attack (TIA), also known as a “mini-stroke.”
3. Management of Peripheral Artery Disease (PAD): It is used to reduce the risk of heart attacks, strokes, and other cardiovascular events in individuals with peripheral artery disease, a condition characterized by narrowed arteries in the legs, arms, stomach, or head.
4. Prevention of Blood Clots: It is prescribed to prevent blood clots in patients undergoing certain cardiovascular procedures, such as coronary artery stent placement or angioplasty.
5. Adjunctive Therapy with Aspirin: Clopidogrel is often used in combination with aspirin for individuals with acute coronary syndrome (ACS), including unstable angina or myocardial infarction (heart attack), to further reduce the risk of cardiovascular events.
6. Secondary Prevention in High-Risk Patients: It also prescribed for long-term use in individuals at high risk of cardiovascular events, such as those with multiple risk factors for heart disease or previous cardiovascular events, to reduce the risk of recurrent events.
7. Myocardial Infarction: It also used to treat myocardial infarction and prevent future attacks.
8. Ischemic Stroke: This medicine is used to treat ischemic stroke and prevent future attacks.
9. Atrial Fibrillation: It prevent stroke and systemic embolism in people with atrial fibrillation.
10. Peripheral Artery Revascularization: It is used to prevent blood clots after peripheral artery revascularization.

Clopidogrel uses in Urdu

دل کی مختلف حالتوں کے لیے ڈاکٹر کلوپیڈوگریل تجویز کرتے ہیں، بشمول، ہارٹ اٹیک، انجائنا، کارڈیک سٹینٹ، اور دیگر جن کی تفصیل ذیل میں دی گئی ہے۔

دل کے حملوں کی روک تھام: کلوپیڈوگریل ان افراد میں دل کے دورے کے خطرے کو کم کرنے کے لیے تجویز کیا جاتا ہے جن میں حالیہ ہارٹ اٹیک یا غیر مستحکم انجائنا (سینے میں درد کی ایک قسم) کی تاریخ ہے۔

فالج کی روک تھام: یہ حالیہ اسٹروک یا عارضی اسکیمک اٹیک کی تاریخ والے لوگوں میں فالج کو روکنے میں مدد کرتا ہے، جسے “منی اسٹروک” بھی کہا جاتا ہے۔

پیریفرل آرٹری ڈیزیز کا انتظام: یہ پیریفرل آرٹری ڈیزیز والے افراد میں ہارٹ اٹیک، فالج اور دیگر قلبی واقعات کے خطرے کو کم کرنے کے لیے استعمال کیا جاتا ہے، یہ حالت ٹانگوں، بازوؤں، پیٹ یا سر میں تنگ شریانوں سے ہوتی ہے۔

خون کے جمنے کی روک تھام: یہ ایسے مریضوں میں خون کے جمنے کو روکنے کے لیے تجویز کیا جاتا ہے جو دل کے بعض طریقہ کار سے گزر رہے ہیں، جیسے کورونری آرٹری سٹینٹ کی جگہ یا انجیو پلاسٹی۔

اسپرین کے ساتھ ملحقہ تھراپی: کلوپیڈوگریل اکثر ایکیوٹ کورونری سنڈروم والے افراد کے لیے اسپرین کے ساتھ استعمال کیا جاتا ہے، بشمول غیر مستحکم انجائنا یا مایوکارڈیل انفکشن (ہارٹ اٹیک)، قلبی واقعات کے خطرے کو مزید کم کرنے کے لیے۔

زیادہ خطرہ والے مریضوں میں ثانوی روک تھام: اسے دل کے واقعات کے زیادہ خطرہ والے افراد میں طویل مدتی استعمال کے لیے تجویز کیا جا سکتا ہے، جیسے کہ دل کی بیماری یا پچھلے قلبی واقعات کے لیے متعدد خطرے والے عوامل، بار بار ہونے والے واقعات کے خطرے کو کم کرنے کے لیے۔

 یہ دل کا دورہ کے علاج اور مستقبل کے حملوں کو روکنے کے لیے بھی استعمال ہوتا ہے۔ :Myocardial infarction

اسکیمک اسٹروک: یہ دوا اسکیمک اسٹروک کے علاج اور مستقبل میں ہونے والے حملوں کو روکنے کے لیے استعمال ہوتی ہے۔

ایٹریل فبریلیشن: یہ ایٹریل فبریلیشن والے لوگوں میں فالج اور سیسٹیمیٹک ایمبولزم کو روکتا ہے۔

پیریفرل آرٹری ریواسکولرائزیشن: اس کا استعمال پیریفرل آرٹری ریواسکولرائزیشن کے بعد خون کے جمنے کو روکنے کے لیے کیا جاتا ہے۔

How to use Clopidogrel

The medications are typically taken orally, and following your healthcare provider’s instructions is important. Here’s a general guide on how to use clopidogrel:

Dosage: Take clopidogrel exactly as prescribed by your doctor. The dosage can vary depending on your medical condition and other factors. Do not change your dose or stop taking clopidogrel without consulting your doctor.

Timing: Clopidogrel is usually taken once a day. It can be taken with or without food. Try to take it at the same time each day to maintain a consistent level of the medication in your body.

Swallow Whole: Swallow the tablet whole with a full glass of water. Do not crush, chew, or break the tablet before swallowing, as this can increase the risk of side effects or affect the medication’s effectiveness.

Do Not Double Dose: If you miss a dose, take it as soon as you remember. However, if it’s almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not double dose to make up for a missed one.

Duration of Treatment: The duration of clopidogrel treatment varies depending on your medical condition and the reason for taking it. Follow your doctor’s recommendations regarding the duration of treatment.

Combination Therapy: If you’re taking clopidogrel in combination with aspirin or other medications, follow your doctor’s instructions precisely. Do not alter the dosage or frequency of any medications without consulting your healthcare provider.

Benefits:

The benefits of clopidogrel include:

1. Reduction of thrombotic events: By inhibiting platelet aggregation, it reduces the risk of heart attacks, strokes, and peripheral vascular events.
2. Improved procedural outcomes: Clopidogrel helps prevent stent thrombosis and restenosis following PCI procedures, enhancing procedural success rates.
3. Enhanced secondary prevention: Long-term clopidogrel therapy reduces the risk of recurrent cardiovascular events, improving overall prognosis.
4. Versatile treatment option: It is effective in various clinical settings, including ACS, PAD, and post-procedural care.
5. Combination therapy benefits: Clopidogrel is often used in combination with aspirin or other antiplatelet medications to achieve greater efficacy in preventing cardiovascular events.

key facts

Here are the key facts about Clopidogrel:

• Clopidogrel is an antiplatelet medicine, which prevents blood cells from sticking together and forming dangerous blood clots.
• The usual dose for clopidogrel is 75mg once a day, and it is often prescribed in conjunction with aspirin.
• Clopidogrel can be taken by adults aged 18 and over.
• The most common side effects of this medicine include easier bleeding and bruising.
• You can drink alcohol while taking clopidogrel but do not drink too much as it can irritate your stomach.
• You may need to stop taking this medicine for a short time before surgery or dental treatment.

Clopidogrel Side Effects

Clopidogrel, a medication used to prevent blood clots and stroke, can cause several side effects, some common and mild, others rare and serious.

Common Side Effects

• Bleeding (bruising, nosebleeds, blood in urine or stool)
• Digestive issues (diarrhea, abdominal pain, indigestion)
• Headache
• Dizziness
• Fatigue
• Rash
• Itching
• Nausea
• Vomiting

Less Common Side Effects

• Chest pain
• High blood pressure
• Insomnia
• Anxiety
• Depression
• Confusion
• Hallucinations
• Seizures
• Muscle weakness
• Joint pain
• Eye problems (vision changes, double vision)

Rare Side Effects

• Severe bleeding (intracranial hemorrhage, gastrointestinal bleeding)
• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic anemia
• Agranulocytosis (low white blood cell count)
• Stevens-Johnson syndrome (severe skin reaction)
• Toxic epidermal necrolysis (severe skin reaction)
• Liver damage (hepatitis, jaundice)

Dosage Adjustments

Adults:

• Acute coronary syndrome (ACS): 75 mg orally once daily
• Peripheral artery disease: 75 mg orally once daily
• Atrial fibrillation (AF): 75 mg orally once daily

Renal impairment:

• Mild to moderate impairment: no adjustment needed
• Severe impairment (CrCl <30 mL/min): reduce dose to 50 mg orally once daily

Hepatic impairment:

• Mild to moderate impairment: no adjustment needed
• Severe impairment: reduce dose to 50 mg orally once daily

Concomitant medications:

• Strong CYP2C19 inhibitors (e.g., omeprazole): reduce dose to 50 mg orally once daily
• Strong CYP2C19 inducers (e.g., rifampin): increase dose to 150 mg orally once daily

Clopidogrel Activation

Clopidogrel is a prodrug, meaning it requires activation in the body to become effective. This activation occurs in two steps:

1. First step: Clopidogrel is oxidized by enzymes such as CYP2C19, CYP1A2, and CYP2B6. This step converts the drug into an intermediate metabolite.
2. Second step: The intermediate metabolite is then further oxidized by enzymes such as CYP2C19, CYP2C9, CYP2B6, and CYP3A. This step converts the intermediate metabolite into the active form of the drug.

Pharmacokinetics

The active metabolite of clopidogrel has a short elimination half-life of approximately 0.5-1.0 hours. This means that the drug is quickly cleared from the body and must be taken regularly to maintain its effects.

CYP2C19 Variant Allele

Some individuals have a variant allele of the CYP2C19 enzyme, which is responsible for activating clopidogrel. This variant allele reduces the efficiency of clopidogrel activation, leading to:

• Reduced efficacy
• Increased risk of complications
• Increased risk of cardiovascular events

This is because the variant allele reduces the amount of active metabolite formed, making the drug less effective at preventing platelet aggregation and blood clot formation.

Drug Interactions

Clopidogrel interacts with many medicines, including:

• Blood thinners (e.g., warfarin, heparin)
• Pain relievers (e.g., Aspirin, NSAIDs)
• Antidepressants (e.g., SSRIs, fluoxetine)
• Antibiotics (e.g., macrolides, rifampin)
• Heart rhythm medicines (e.g., amiodarone, quinidine)
• Stomach acid reducers (e.g., proton pump inhibitors)

Taking clopidogrel with these medicines can increase the risk of bleeding or reduce the effectiveness of this medicine. It’s important to tell your doctor about all medicines you’re taking to avoid potential interactions.

Who can and cannot take clopidogrel

Who can take clopidogrel:

• Patients with heart disease, recent heart attack, recent stroke, or peripheral vascular disease.
• Patients with acute coronary syndrome.
• Patients with chest pain.
• Patients with peripheral artery disease.

Who cannot take clopidogrel:

• Patients with active bleeding, such as brain bleed or stomach ulcer.
• Patients allergic to thienopyridines.
• Patients with a history of thrombotic thrombocytopenic purpura (TTP).
• Patients with severe liver disease.
• Children younger than 18 years.
• Breastfeeding women (due to unknown effects on infant).

Forms and Strengths, of Clopidogrel

It is available in oral tablet form and is commonly marketed under the brand name Plavix. It is manufactured by various pharmaceutical companies worldwide. The tablets come in different strengths to accommodate varying dosages prescribed by healthcare providers.

Oral Tablets: Clopidogrel tablets are available in the following strengths:

• 75 mg: This is the most common strength of clopidogrel tablets prescribed for the prevention of cardiovascular events such as heart attacks and strokes. It is typically taken once daily.
• 300mg: This higher-strength tablet may be used as a loading dose in certain clinical situations, such as in patients undergoing percutaneous coronary intervention (PCI) or as directed by a healthcare provider.

Brand Name: The most widely recognized brand name for clopidogrel is Plavix. Plavix is available in both the 75 mg and 300 mg strengths and is manufactured by various pharmaceutical companies.

Clopidogrel tablet price

Plavix -75mg, also known as clopidogrel, is available for 1266 rupees in Pakistan.

Special Precautions and Warnings

Bleeding Risk:

• Increased risk of bleeding, including severe or life-threatening bleeding
• Be cautious when using sharp objects, razors, or engaging in activities that increase bleeding risk

Pregnancy and Breastfeeding:

• Use during pregnancy only if clearly needed
• Do not breastfeed while using clopidogrel

Genetic Factors:

Reduced effectiveness in patients with certain genetic factors (CYP2C19 poor metabolizers)

Surgery and Dental Procedures:

Inform your doctor or dentist that you are taking clopidogrel before any procedures

Drug Interactions:

Avoid concurrent use with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, heparin, and selective serotonin reuptake inhibitors (SSRIs)

Liver Disease:

Use with caution in patients with severe liver disease

Thrombotic Thrombocytopenic Purpura (TTP):

Monitor for signs of TTP, such as bruising, petechiae, or bleeding

Clopidogrel Brands in Pakistan

Plavix – Sanofi Aventis (Pakistan) Ltd.

Clopivax – Ethical Laboratories (Pvt) Ltd.

Ogrel – Bosch Pharmaceuticals (Pvt) Ltd.

Clogrel – Pharmatec Pakistan (Pvt) Ltd.

Platlo – High – Q International

Clopidro – Pearl Pharmaceuticals

Extrac – Asian Continental (Pvt) Company

Isteblix – Pfizer Laboratories Ltd.

Lowplat – Pharmevo (Pvt) Ltd.

Seaclop – Searle Pakistan (Pvt.) Ltd.

Conclusion

Clopidogrel, a widely used antiplatelet medication, plays a crucial role in preventing blood clots in individuals at high risk of cardiovascular events such as heart attacks and strokes. It is particularly beneficial for patients with a history of acute coronary syndrome, peripheral artery disease, or those undergoing percutaneous coronary interventions. By inhibiting platelet aggregation, It significantly reduces the risk of thrombotic events, thereby improving cardiovascular outcomes.