CLOPEX is used to reduce the risk of acute heart attacks. This medicine contains the active ingredient clopidogrel, which prevents blood clots and reduces the likelihood of strokes. In this article, we will review the uses of the medicine and its instructions for use through the Dalili Medical website.

 

Does CLOPEX cause constipation?

 

Taking CLOPEX can cause constipation in some people as a side effect, but this does not mean that all users will experience this problem.

Does CLOPEX cause headaches?

 

Headaches and dizziness are common side effects associated with the use of CLOPEX.

Does CLOPEX cause vomiting?

 

Some users may feel nauseous or vomit when taking this medicine, as these side effects are among the possible effects of Clobex 75.

**Indications for use of Clobex**

 

Clobex is used to prevent blood clots in the blood vessels, especially in people who are more susceptible to this condition, such as:

- Heart attacks.

- Angina.

- Strokes.

- Peripheral arterial disease.

- After cardiovascular surgery.

**Indications for use of Aspirin Protect 100**

 

Aspirin tablets are used in low or medium doses to relieve pain and reduce fever, in addition to treating colds. In high doses, they can help reduce the symptoms of:

- Rheumatic fever.

- Rheumatic arthritis.

- Other inflammatory joint diseases.

**Low dose uses:**

 

Low doses of the drug are used in the following cases:

- Preventing blood clots to reduce the risk of angina.

- Preventing myocardial infarction in patients with cardiovascular disease.

- Preventing stroke.

**Indications for use of Clobex:**

 

Clobex 75 mg is used to prevent blood clots in blood vessels, especially in the arteries, which helps avoid atherosclerosis and the resulting strokes or heart attacks that may lead to death.

**Clobex to prevent stroke:**

 

Strokes are serious, life-threatening conditions that occur as a result of interruption of blood supply to the brain, which deprives cells of the necessary food and oxygen. This interruption may damage parts of the brain or threaten the life of the individual.

Clobex is used, especially with aspirin, to protect patients who have had a previous stroke from recurring, for a period of up to 3 months.

**Pregnancy and lactation:**

 

**Pregnancy:** This drug has not been classified for safety during pregnancy by the US Food and Drug Administration, while it has been classified as category B1 by the Australian Therapeutic Goods Administration, indicating that the risk of its use is considered low. Available data from published cases and post-marketing surveillance have not shown any association between the use of this drug during pregnancy and the occurrence of major birth defects, miscarriages, or harm to the fetus. Although this drug can cross the placenta, animal studies have not shown any evidence of harm to the fetus. Reproduction studies in mice and rabbits at doses up to 500 and 300 mg/kg/day (equivalent to 65 and 78 times the recommended daily human dose, respectively, based on mg/m²) have shown no evidence of impaired fertility or fetal toxicity. There are no data available on human pregnancy monitoring.

**Clopex and Coronary Artery Disease**

 

Coronary artery disease involves the buildup of plaque in the arteries that supply oxygen-rich blood to the heart, which can lead to narrowing or blockage, and thus the patient may be exposed to a heart attack. Clopex is useful for patients with coronary artery disease, as it helps reduce the risk of clots, and is more effective when used with aspirin than using aspirin alone.

**Clopex and heart attacks**

 

Heart attacks (myocardial infarction) occur when blood does not reach some parts of the heart, which leads to damage to the heart muscle as a result of this continued interruption. Coronary artery disease is one of the main causes of heart attacks. Clopex is used as a means of preventing heart attacks, and to prevent blood clots and blockages of the arteries resulting from heart disease and coronary artery disease.

**Childbirth:** Treatment should be stopped 5-7 days before the start of labor or delivery or spinal anesthesia. Using the treatment during labor or delivery may increase the risk of bleeding. It is preferable to avoid spinal anesthesia while taking Clopidogrel due to the possibility of spinal hematoma.

**Breastfeeding:** This drug has been used during lactation without apparent harmful effects. The drug passes into breast milk in animals, and it is likely that this also occurs in humans. Therefore, it should be used with caution during lactation, taking into account that the benefit of its use is greater than the potential risks.

**Dose and method of use of Clopex**

 

**Timing:** It can be taken with or without food.

**Adults:**

**Usual dose for the treatment of acute coronary syndrome** (such as unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction):

- **High initial dose (loading dose):** 300 mg taken orally once.

- **Maintenance dose (maintenance dose):** 75 mg taken orally once daily.

**Duration of treatment:** It may last up to 12 months, but the optimal duration is not specified.

It should be noted that starting treatment without the doseThe large initial dose will delay the effect of the antiplatelet drug for several days.

**In the case of the elderly (over 75 years):** The large initial dose is not given.

The drug is used in cases of myocardial infarction associated with ST-segment elevation.

This drug is taken with aspirin at a dose ranging from 75 mg to 325 mg orally once daily.

Uses: It is intended to prevent the occurrence of blood clots resulting from atherosclerosis (thrombotic events) in patients with acute coronary syndromes without ST-segment elevation, such as unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI). It is also used in patients who require drug treatment or who will undergo coronary revascularization procedures, in addition to cases of myocardial infarction associated with ST-segment elevation (STEMI).

The usual adult dose for the treatment of coronary artery disease, ischemic stroke, and peripheral arterial disease is:

75 mg orally once daily.

**Uses:**

- **Prevention of atherosclerotic strokes (thrombotic events):** For use in patients with a recent history of heart attack, stroke, or active peripheral arterial disease.

- **Secondary prevention of mini-stroke or transient ischemic stroke (TIA):** It is recommended to consider combining clopidogrel with aspirin within 24 hours of a mini-stroke or TIA, and continue for 21 days.

- **Secondary prevention of intracranial atherosclerosis (70% to 99% narrowing of a major intracranial artery):** Clopidogrel and aspirin are recommended for use together for 90 days in patients who have had a mini-stroke or TIA within 30 days due to severe 70% to 99% narrowing of a cerebral blood vessel.

- **Usual adult dose for prevention of stroke resulting from a clot coming from the heart (Cardioembolic Stroke):** It is used as prophylaxis if the patient is unable to be treated with oral anticoagulants. The dose is 75 mg orally daily.

**Recommended adult dose for carotid artery stenting - Non-prescription use:**

 

- **Initial dose (loading dose):** 300 mg orally, plus aspirin at a dose of 81 to 325 mg once daily, prior to carotid artery stenting.

- **Maintenance dose:** 75 mg orally daily, with aspirin 81 to 325 mg daily for at least 30 days after stenting.

- **Alternative dosage regimen:** 300 to 600 mg orally once, followed by 75 mg daily for 4 days prior to carotid stenting, with aspirin 81 to 325 mg daily.

**Usual adult dose for percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS):** Includes conditions such as non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI).

Followed by 75 mg once daily (in combination with aspirin) for at least 12 months (for bare metal or drug-eluting stents), a higher dose of 150 mg once daily for 6 days, then 75 mg once daily thereafter may be considered.

Usual Adult Dose for Percutaneous Coronary Intervention (PCI) for Non-Acute Coronary Syndrome (i.e., stable ischemic heart disease) (Off-label Use):

High Initial Dose (Loading Dose): 600 mg given as soon as possible before or at the time of PCI.

Followed by 75 mg once daily (in combination with aspirin) for at least 1 month for bare metal or 6 months for drug-eluting stents.

Usual Adult Dose for Secondary Prevention After Coronary Artery Bypass Graft Surgery (CABG) (Off-label Use): (American Heart Association Kulik 2015)

After off-pump CABG: 75 mg once daily (with aspirin) for 1 year.

Patients who are allergic to or intolerant of aspirin: 75 mg once daily without aspirin; continue for life.

Usual Adult Dose After Peripheral Artery Percutaneous Transluminal Angioplasty (with or without stenting) or Peripheral Artery Bypass Graft Surgery (Off-label Use):

75 mg orally once daily.

In below-knee bypass graft surgery with prosthetic grafts, it is used in combination with aspirin at a dose of 75 to 100 mg/day.

Usual Adult Dose for Transcatheter Aortic Valve Replacementt (TAVR) (for prevention of blood clots Thromboprophylaxis) (off-label use): Oral:

**Before the procedure:**

 

- For those not taking clopidogrel: 300 mg on the day of the procedure.

- For those taking clopidogrel: 75 mg once daily should be continued before the procedure.

**After the procedure:**

- For patients who will not take anticoagulant medications after the procedure: Clopidogrel 75 mg once daily for 3 to 6 months, depending on the type of valve and the risk of bleeding or clotting, in addition to taking aspirin for life.

**Children:**

Usual pediatric dose for antiplatelet effect (limited data available):

**Infants and children 24 months of age and younger:** The recommended dose is 0.2 mg/kg once daily, to achieve a similar level of platelet aggregation inhibition to adults receiving the recommended dose, according to the results of the PICOLO trial. It should be noted that this study included pediatric patients with a corporal arteriopulmonary bypass, intracardiac or vascular stent, Kawasaki disease, or an arteriovenous flap. 79% of patients received concomitant aspirin (Lee 2008).

**Children 2 years of age and adolescents:** The initial dose is 1 mg/kg once daily, and the dose may be increased until the desired response is achieved. In general, the recommended dose for adults should not be exceeded (Finkelstein 2005; Soman 2006).

**Patients with impaired metabolism due to CYP2C19 enzyme (e.g. CYP2C19 *2 or *3 carriers):** There are no special recommendations for children. Based on clinical experience with adult patients, genetic testing is not recommended as a routine for patients receiving treatment with the drug (clopidogrel).

**Preparations as a pharmaceutical formulation:**

 

A 5 mg/ml syrup (suspension) can be prepared using tablets. Four 75 mg tablets are crushed and turned into a fine powder. Then a small amount of a 1:1 mixture of Ora-Sweet® and Ora-Plus® is added, and mixed well to make a homogeneous paste. While adding the solvent, the paste is mixed to form approximately 60 ml. The mixture is transferred to a measuring bottle, and enough solvent is added to reach 60 ml. A label stating “Shake before use” must be placed. The product is stable and usable for 60 days at room temperature or in the refrigerator.

**Dose adjustment in case of kidney disease:**

 

**Dose adjustment in case of liver disease:**

No dose adjustment is necessary.

**Precautions:**

**Missed dose:** If the missed dose is less than 12 hours from the scheduled time, it should be taken immediately. If more than 12 hours have passed, the missed dose should be skipped and the next regularly scheduled dose should be taken. Two doses of this medicine should not be taken at the same time.

**Dietary considerations:** It is recommended to avoid or reduce the consumption of grapefruit juice.

**Effect of the medicine in patients with poor metabolism:**

The effectiveness of this medicine depends on its breakdown into an active breakdown product (metabolite) by the CYP450 enzyme, particularly the CYP450 2C19 enzyme.

Patients with poor activity of the CYP450 2C19 enzyme, when taking the recommended doses, show a lesser effect of the medicine on platelet activity than patients with normal function of this enzyme.

Although a higher dosing regimen (600 mg as a loading dose followed by 150 mg daily) in poor metabolizers may increase the antiplatelet effect of the drug, no appropriate dosing regimen has been established for these patients in clinical trials.

Assays to determine the CYP450 2C19 genotype are available and may be used as an aid in determining the appropriate therapeutic strategy.

Alternative treatment options or other therapeutic strategies should be considered for patients with impaired CYP450 2C19 activity.

Platelets affected by the breakdown products of the active drug remain under the influence of the drug for the remainder of their life span, which is 7 to 10 days. The body recovers normal platelet function at a rate consistent with the rate of platelet turnover.

**Patient advice**

- Patients should be informed of the increased risk of bleeding and bruising, and should report any unexpected, persistent or excessive bleeding, or blood in the stool or urine.

- Patients are advised to inform all healthcare providers, including dentists, that they are taking this medication, due to the increased risk of bleeding during surgery and dental procedures.

- Patients should talk to their doctor if they are taking any prescription or over-the-counter medications.

- Patients should be warned of the symptoms of TTP and seek medical attention immediately if they occur.

**Side effects: The most prominent**

**Common (1: 10%):**

- Upper respiratory tract infection (8.7%)

- Chest pain (8.3%)

- Headache (7.6%)

- Cold-like syndrome (7.5%)

- Arthralgia (6%)

- Pain (6%)

- Dizziness (6%)

- Diarrhea (4.5%)

- Rash (4.2%)

- Rhinitis (4.2%)

- Depression (3.6%)

- Urinary tract infection (3.1%)

**Uncommon (<1%):**

- Severe neutropenia (a type of white blood cell)

- Thrombotic thrombocytopenic purpura

- Acute liver failure

- Aplastic anemia

- Low blood pressure

- Hepatitis

- Myalgia

- Eczema (allergic dermatitis)

- Erythema For the skin

- Agranulocytosis (a type of white blood cell)

The following conditions have been reported after using the medicine:

**Blood and respiratory system disordersLymphocytic:** Agranulocytopenia (a type of white blood cell), pancytopenia, aplastic anemia, and thrombotic thrombocytopenic purpura, as well as acquired hemophilia A.

**Eye disorders:** Bleeding into the eye, including conjunctiva and retina.

**Gastrointestinal disorders:** Gastrointestinal and retroperitoneal bleeding, which can be fatal, as well as colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis, gastric or duodenal ulcer, and diarrhea.

**General disorders:** Fever and bleeding from the surgical wound.

**Hepatobiliary disorders:** Acute liver failure, non-infectious hepatitis, and liver dysfunction.

**Immune system disorders:** Allergic reactions, anaphylaxis, and serum sickness.

**Musculoskeletal disorders:** Musculoskeletal bleeding, myalgia, arthralgia, and arthritis.

**Nervous system disorders:**

Psychiatric disorders: include decreased awareness and hallucinations.

Respiratory and chest disorders: include bronchoconstriction (spasm), interstitial pneumonia, respiratory tract bleeding, and eosinophilic pneumonia.

**Kidney and urinary tract disorders:** Elevated creatinine levels.

**Skin and subcutaneous tissue disorders:**

 

- Maculopapular rash

- Erythematous

- Exfoliative

- Urticaria

- Bullous dermatitis

- Eczema

- Toxic epidermal necrolysis

- Stevens-Johnson syndrome

- Angioedema

- Drug-induced hypersensitivity syndrome

- Drug rash with eosinophilia and systemic symptoms (DRESS)

- Erythema multiforme

- Skin bleeding

- Lichen planus

- Itching all over the body

- Acute generalized pustular rash (Acute generalized exanthematous pustulosis (AGEP)

**Vascular disorders:** include vasculitis and hypotension.

**Precautions for use:**

The reduced effect of the drug in patients with poor metabolism results in a reduction in its active breakdown products (metabolites). The effectiveness of this drug depends on its breakdown into an active metabolite by the CYP450 enzyme, particularly CYP450 2C19.

Patients with impaired CYP450 2C19 function who receive the recommended doses show a reduced effect of the drug on platelet activity compared to patients with normal CYP450 function.

Although the use of a higher dose regimen (600 mg as a loading dose followed by 150 mg daily) in patients with poor metabolism increases the antiplatelet effect of the drug, an appropriate dosage regimen for these patients has not been determined in clinical trials.

Tests to determine the CYP450 2C19 genotype are available and can be used as an aid in determining the appropriate therapeutic strategy.

Alternative therapies or different therapeutic strategies should be considered for patients with impaired CYP450 2C19 activity.

Caution should be exercised when using the treatment in patients with bleeding or platelet disorders.

Premature discontinuation of treatment may increase the risk of cardiovascular events; therefore, it is recommended to discontinue treatment 5 days prior to any elective surgery that carries a significant risk of bleeding.

Caution should be exercised in patients with atrial fibrillation, and the risk of bleeding should be carefully evaluated; a significant increase in serious bleeding has been reported in patients receiving clopidogrel with aspirin compared to aspirin alone.

For patients with aspirin sensitivity who are undergoing therapeutic cardiac catheterization (PCI), it is advisable to refer to the recommendations of the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the American College of Cardiology (ACC).

Rare cases of thrombotic thrombocytopenic purpura (TTP) have been reported in association with the use of this drug, which can be fatal.

Risk of bleeding, which can lead to death.

Liver or renal impairment.

Cross-allergic reactions, including rash, angioedema, or hematologic adverse events, have been reported with the use of thienopyridines (eg, ticlopidine and prasugrel). Therefore, patients with a history of anaphylaxis should be evaluated.

Caution should be exercised in patients with severe hepatic or renal impairment.

Use with caution or avoid in patients with a history of hypersensitivity or hematologic adverse events from previous use of thienopyridine drugs, including ticlopidine and prasugrel.

Caution should be exercised in patients receiving anticoagulants, such as heparin and warfarin, or other platelet aggregation inhibitors, as the risk of bleeding may be increased.

Premature discontinuation of treatment may result in stent thrombosis, which may cause fatal or non-fatal myocardial infarction. The duration of treatment depends on the type of stent used.

May increase the risk of major bleeding in patients who have had a recent lacunar stroke.

Inhibition of CYP2C19 in patients with poor drug metabolism may reduce the production of active metabolites.

The metabolism of clopidogrel to its active metabolite may be affected by genetic changes in the CYP2C19 enzyme.

Clopidogrel is a prodrug (inactive) and requires CYP2C19 to be converted to its active metaboliteActive acceptance; inhibition of platelet aggregation is entirely dependent on the active metabolite of clopidogrel.

Genetic variations in the CYP2C19 enzyme, such as CYP2C19 *2 and CYP2C19 *3, do not result in the conversion of clopidogrel to its active metabolite; while genetic variations in CYP2C19 *4, *5, *6, *7, and *8 may be associated with decreased or absent metabolism of clopidogrel to its active metabolite, but are less common than CYP2C19 *2 and *3.

More than 50% of Asians carry genetic variations in the CYP2C19 enzyme that impair the metabolism of clopidogrel to its active metabolite.

Use of CYP2C19 inhibitors (such as proton pump inhibitors [PPIs]) or use by patients with poor metabolism can exacerbate this problem.

**Drug interactions:**

To avoid potential interactions with other medications, it is essential to inform your doctor or pharmacist about all medications that are currently being taken. The most important of these interactions are:

**Proton pump inhibitors (PPIs):** The use of CYP2C19 inhibitors, such as proton pump inhibitors, or their use by patients with poor drug metabolism, may reduce the production of active metabolites, which negatively affects the effectiveness of the antiplatelet drug. Observational studies, in addition to one randomized clinical trial, have shown that the concomitant use of clopidogrel with proton pump inhibitors has negative effects on cardiovascular outcomes.

**Ombitasvir / Paritaprevir / Ritonavir & Dasabuvir:** Clopidogrel can increase the level or effect of ombitasvir / paritaprevir / ritonavir and dasabuvir by reducing their rate of breakdown. Therefore, it is advisable to avoid this use. Studies have shown that strong CYP2C8 inhibitors increase the plasma concentrations of dasabuvir by approximately 10-fold, increasing the risk of Q interval prolongation.

Drugs with antiplatelet properties, such as aspirin, P2Y12 inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective serotonin reuptake inhibitors (SSRIs), may enhance the antiplatelet effect. Careful monitoring of treatment is important.

Anticoagulants such as antithrombin alpha, antithrombin III, apixaban, argatroban, bivalirudin, dalteparin, fondaparinux, lepirudin, and tinzaparin are drugs with anticoagulant properties. Drugs that affect platelets such as clopidogrel may enhance the effect of anticoagulants. Care should be taken to exclude some drugs such as bemiparin, enoxaparin, and heparin, and to monitor treatment periodically.

Strong CYP2C19 inducers such as carbamazepine, rifabutin, rifampin, and St. John's wort may increase the concentrations of the active metabolite of clopidogrel, which may enhance its efficacy. Therefore, treatment should be carefully monitored.

Moderate or strong CYP2C19 inhibitors such as cimetidine, clarithromycin, efavirenz, eslicarbazepine acetate, esomeprazole, erythromycin, etravirine, felbamate, fluconazole, fluoxetine, fluvoxamine, isoniazid, ketoconazole, modafinil, nefazodone, omeprazole, oxcarbazepine, rabeprazole, ticlopidine, and voriconazole may decrease the blood concentrations of the active metabolite of clopidogrel.

Therefore, caution should be exercised when using any moderate CYP2C19 inhibitor in patients receiving clopidogrel, due to the risk of reduced efficacy of this drug. Patients should be monitored carefully for signs of reduced response to clopidogrel, and it may be appropriate to consider modifying the treatment plan.

**Morphine:** Decreases the level or effect of clopidogrel. Taking morphine with opioid analgesics delays and reduces the absorption of clopidogrel, thought to be due to slower gastric emptying, resulting in reduced exposure to the active metabolites of clopidogrel. Therefore, it is advisable to consider the use of intravenous antiplatelet agents in patients with acute coronary syndrome who require concomitant administration of morphine or other opioid analgesics.

**Protamine:** Protamine and clopidogrel potentiate each other through synergism. Therefore, concomitant use is contraindicated because it increases the risk of bleeding.

Repaglinide: Clopidogrel can increase the level or effect of repaglinide. Clopidogrel inhibits the enzyme CYP2C8, which can lead to significant increases in blood levels of repaglinide when used together. If it is necessary to take both drugs together, it is recommended to reduce the initial dose of repaglinide to 0.5 mg per meal, and not to exceed 4 mg per day.