Generality
Clopidogrel is an active antiplatelet agent used to prevent thrombus formation.
From the chemical point of view, clopidogrel belongs to the thienopyridine family. It is an active ingredient which, to perform its therapeutic action, must be administered orally . However, it should be pointed out that clopidogrel is capable of inhibiting platelet aggregation only after its transformation into its active metabolite by cytochrome P450 enzymes (CYP450). In other words, clopidogrel is a prodrug which, to carry out its activity, must first be metabolised by the organism.
Examples of Specialties Medicinal products containing Clopidogrel
- Averelix®
- Clopidogrel DOC Generici®
- Clopidogrel Teva®
- Duoplavin®
- Grepid®
- Iscover®
- Nogreg®
- Plavix®
- Revlis®
- Zopya®
- Zyllt®
Therapeutic indications
When is the use of clopidogrel indicated?
The use of clopidogrel is indicated in adult patients to prevent the formation of blood clots ( thrombi ) in case of:
- Hardening of arterial vessels (atherosclerosis) with consequent heart attack, stroke or peripheral arterial disease;
- Previous episode of unstable angina or myocardial infarction;
- Presence of atrial fibrillation in patients who cannot take vitamin K antagonists (oral anticoagulants).
Did you know that ...
Clopidogrel can be used in the above mentioned conditions either alone or in combination with acetylsalicylic acid (another antiplatelet agent). In this regard, we note the presence on the pharmaceutical market of medicinal products containing both the aforementioned active ingredients.
Warnings
Warnings and Precautions for the use of Clopidogrel
Before starting clopidogrel therapy, you must tell your doctor if you are in one or more of the following conditions:
- You are exposed to a high risk of bleeding or hemorrhage caused, for example, by:
- Presence of gastrointestinal ulcers;
- Presence of diseases or blood disorders that may predispose to bleeding;
- Presence of recent severe wounds;
- One must undergo, or have just undergone, surgery (including dental surgeries);
- An ischemic stroke has occurred in the last seven days;
- You suffer from liver and / or kidney diseases;
- Allergic reactions have developed following the use of other antiplatelet agents or oral anticoagulants.
In any case, as a precautionary measure, before taking clopidogrel-based medicines, it is always a good idea to inform your doctor of your health conditions and of the possible presence of any type of disorder or illness.
Furthermore, your doctor should be contacted immediately and informed if you are in one or more of the following situations during treatment with clopidogrel:
- Occurrence of symptoms such as bruises, fever and fatigue, since it could be a thrombotic thrombocytopenic purpura (a possible side effect of treatment with clopidogrel);
- If you seriously injure yourself, as the risk of bleeding increases;
- If you have to undergo surgery of any kind (even in an outpatient setting).
Please note
Taking clopidogrel could lead to side effects that could affect the ability to drive and / or operate machinery, therefore caution is advised.
Pharmacological Interactions
Interactions of Clopidogrel with Other Drugs
Because of the drug interactions that could occur, before taking clopidogrel you need to tell your doctor if you are taking - or have recently been taken - drugs such as:
- Drugs capable of increasing the risk of bleeding and / or bleeding, such as:
- Other antiplatelet agents ;
- Oral anticoagulants ;
- Heparin or other injectable anticoagulants ;
- Non-steroidal anti-inflammatory drugs ( NSAIDs );
- Serotonin selective reuptake inhibitors ;
- Proton pump inhibitor drugs (for example, omeprazole, esomeprazole, etc.);
- Antiviral drugs used in the treatment of HIV (for example, efavirenz);
- Anti- cancer drugs (for example, paclitaxel);
- Antidiabetic drugs such as repaglinide;
- Antifungal drugs (such as fluconazole, voriconazole, etc.);
- Antiepileptic drugs such as carbamazepine;
- Antidepressant drugs inhibiting monoamine oxidase type A ( IMAO-A ) such as moclobemide.
However, before starting clopidogrel therapy, you should still tell your doctor if you are taking - or if you have recently been - drugs or products of any kind, including non-prescription drugs (SOPs), or OTC drugs, herbal and herbal products and homeopathic products.
Side effects
Side effects caused by clopidogrel intake
Like any other active ingredient, clopidogrel can also cause side effects after taking it, although not all patients get them or manifest them in the same way. In fact, each individual reacts subjectively to the intake of the active ingredient. However, the main side effects that could occur during clopidogrel therapy are listed below.
Bleeding and bleeding
Treatment with clopidogrel could cause bleeding and bleeding on various organs and tissues. More in detail, we could see the appearance of:
- Intracranial bleeding;
- Gastrointestinal bleeding;
- Retroperitoneal hemorrhage;
- Intraocular bleeding;
- Epistaxis;
- Hemoptysis and / or pulmonary hemorrhage;
- hematuria;
- Musculoskeletal bleeding;
- Skin bleeding.
Blood and blood and lymphatic system disorders
Treatment with clopidogrel may cause the appearance of:
- Thrombocytopenia;
- Leukopenia, neutropenia or eosinophilia;
- Thrombotic thrombocytopenic purpura;
- Aplastic anemia.
Cardiovascular disorders
Taking clopidogrel could lead to the onset of:
- Hematoma;
- Hypotension;
- vasculitis;
- Kounis syndrome.
Nervous system disorders
Clopidogrel therapy could cause dizziness, headache, dysgeusia and paraesthesia.
Disorders of the gastrointestinal tract
Treatment with clopidogrel may cause:
- Abdominal pain;
- Dyspepsia;
- Diarrhea or constipation;
- Flatulence;
- Nausea and / or vomiting;
- Gastritis;
- Gastric ulcer and duodenal ulcer;
- Ulcerative or lymphocytic colitis;
- Pancreatitis;
- Stomatitis.
Lung and airway disorders
Clopidogrel therapy may promote the onset of bronchospasm, interstitial pneumonia or eosinophilic pneumonia.
Skin and subcutaneous tissue disorders
During treatment with clopidogrel may occur:
- Itch;
- Skin eruptions;
- Bullous dermatitis;
- Urticaria;
- Eczema;
- Stevens-Johnson syndrome;
- Acute generalized exanthematous pustulosis (AGEP).
Other side effects
Other side effects that may occur following the intake of clopidogrel consist of:
- Allergic reactions, even serious, in sensitive individuals;
- Dizziness;
- Gynecomastia;
- glomerulonephritis;
- Increased creatinemia;
- Temperature;
- Arthralgia and / or myalgia;
- Acute liver failure;
- Hepatitis;
- Alteration of liver function tests;
- Increased bleeding time.
Overdose
The intake of excessive doses of clopidogrel may favor the appearance of bleeding and consequent bleeding complications . Therefore, in case of an overdose of clopidogrel - ascertained or presumed - it is necessary to contact the doctor immediately or go to the nearest emergency room bringing with him the packaging of the medicinal product taken. At present, there are no specific antidotes for clopidogrel overdose, therefore treatment is generally symptomatic and supportive.
Action mechanism
How does Clopidogrel work?
As mentioned, clopidogrel is a prodrug which, to carry out its therapeutic action, must first be converted into its active metabolite . This conversion occurs following metabolism by cytochrome P450 enzymes (CYP450). The active metabolite of the clopidogrel thus obtained is able to selectively and irreversibly inhibit the binding of adenosine diphosphate (ADP) with the P2Y12 receptor present at the platelet level. When this receptor is activated by binding to the endogenous ADP substrate, platelet aggregation is favored. Therefore, through the inhibition of the link between ADP and the P2Y12 receptor, the active metabolite of clopidogrel is able to exert an anti-platelet aggregation action.
Did you know that ...
Since the antiplatelet action is due to the active metabolite of clopidogrel whose formation depends on the activity of CYP450, it is possible that not all patients reach an adequate level of inhibition of platelet aggregation. Indeed, some enzymes contained in the cytochrome P450 are polymorphic or may be subject to inhibition by substances, natural products or other medicines taken by the patient. For this reason, it is always good to tell the doctor which medicines or natural products are being taken or have recently been taken.
Method of use and Posology
How to take Clopidogrel
Clopidogrel is available as an oral tablet . These tablets should be swallowed whole with a little water, preferably at the same time each day, with or without food.
Generally, the recommended clopidogrel dose is 75 mg per day.
In case of unstable angina or heart attack, the initial dose can be increased up to 300 mg of active ingredient per day, to be taken in a single dose, or in four divided doses of 75 mg each. After that, the dose can be decreased to 75 mg of clopidogrel per day.
However, the exact amount of clopidogrel that each patient will have to take will be determined by the doctor on an individual basis. This health figure will also decide the duration of the treatment.
Please note
If you forget to take a dose of clopidogrel at the same time of day, it can be taken as long as no more than 12 hours have elapsed since your usual intake time. If more than 12 hours have passed, on the other hand, the next dose should be taken and a double dose should NOT be taken to compensate for forgetfulness.
Pregnancy and breastfeeding
Can Clopidogrel be taken during pregnancy and during breastfeeding?
The use of clopidogrel is not recommended during gestation and even less during breast-feeding. Therefore, if therapy based on the aforementioned active ingredient is necessary, pregnant women (known or suspected) and breastfeeding mothers must necessarily inform the doctor of their situation.
Contraindications
When Clopidogrel should not be used
Clopidogrel should not be used in the following cases:
- In the presence of known hypersensitivity to clopidogrel itself or to any of the excipients contained in the medicinal product to be used;
- In case of bleeding in progress (for example, presence of gastric ulcer, cerebral haemorrhages, etc.);
- In the presence of severe liver disease.
