Clopidogrel Krka d.d.: Uses, Dosage & Side Effects
Antiplatelet agent – thienopyridine P2Y12 ADP-receptor antagonist for prevention of atherothrombotic events
Quick facts about Clopidogrel Krka d.d.
Key Takeaways
- Clopidogrel is an antiplatelet prodrug that irreversibly inhibits the P2Y12 ADP receptor on platelets, preventing platelet aggregation and reducing the risk of atherothrombotic events such as heart attack and stroke.
- The CURE trial demonstrated that adding clopidogrel to aspirin significantly reduces cardiovascular death, non-fatal MI, and stroke in patients with acute coronary syndromes compared to aspirin alone.
- Clopidogrel requires hepatic activation primarily by the CYP2C19 enzyme; patients who are CYP2C19 poor metabolisers may have reduced antiplatelet effect and should be considered for alternative agents (prasugrel or ticagrelor).
- The standard maintenance dose is 75 mg once daily, with or without food; some indications require a 300–600 mg loading dose for rapid onset of antiplatelet effect.
- Clopidogrel Krka d.d. is a bioequivalent generic version of Plavix, meeting the same EMA quality, safety and efficacy standards at typically lower cost.
What Is Clopidogrel Krka d.d. and What Is It Used For?
Quick Answer: Clopidogrel Krka d.d. is a prescription antiplatelet medicine containing clopidogrel 75 mg. It prevents blood clots by irreversibly blocking the P2Y12 ADP receptor on platelets. It is used to reduce the risk of heart attack, stroke, and vascular death in patients with atherosclerotic cardiovascular disease, and as part of dual antiplatelet therapy after coronary stent placement.
Clopidogrel is one of the most important and widely used cardiovascular medicines in the world. It belongs to the thienopyridine class of antiplatelet agents and has been a cornerstone of cardiovascular medicine since the original brand, Plavix (manufactured by Sanofi), gained regulatory approval in 1997. Clopidogrel Krka d.d. is a generic version manufactured by KRKA, a major European pharmaceutical company based in Slovenia, and contains the same active ingredient in the same dose as the original brand product.
Clopidogrel is classified as a prodrug, meaning it is inactive in its administered form and must be metabolised in the liver to produce its active thiol metabolite. This active metabolite then selectively and irreversibly binds to the P2Y12 subtype of adenosine diphosphate (ADP) receptor on the surface of platelets. ADP is one of the key chemical signals that triggers platelet activation and aggregation – the process by which platelets clump together to form a blood clot (thrombus). By permanently blocking this receptor, clopidogrel prevents ADP-mediated platelet aggregation for the entire remaining lifespan of the affected platelet, which is approximately 7–10 days.
The clinical significance of clopidogrel was established through several large-scale randomised controlled trials. The CAPRIE trial (Lancet, 1996) compared clopidogrel with aspirin in over 19,000 patients with atherosclerotic vascular disease and found clopidogrel to be slightly more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, and vascular death. The landmark CURE trial (NEJM, 2001) demonstrated that adding clopidogrel to aspirin (dual antiplatelet therapy, DAPT) in patients with acute coronary syndromes without ST-elevation significantly reduced the rate of cardiovascular death, non-fatal MI, and stroke compared to aspirin alone.
Clopidogrel is listed on the WHO Model List of Essential Medicines, reflecting its importance in global healthcare. It is approved and widely used across all major regulatory jurisdictions, including the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and national regulatory authorities worldwide.
Approved Indications
Clopidogrel is approved for the following clinical indications, as reflected in the EMA-approved Summary of Product Characteristics (SmPC) and the FDA label:
- Secondary prevention of atherothrombotic events: In adult patients suffering from myocardial infarction (from a few days up to less than 35 days), ischaemic stroke (from 7 days up to less than 6 months), or established peripheral arterial disease.
- Acute coronary syndrome (ACS): In combination with aspirin in adult patients with non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction), including patients managed medically and those undergoing percutaneous coronary intervention (PCI) with or without stent placement, or coronary artery bypass graft (CABG) surgery.
- ST-segment elevation acute myocardial infarction (STEMI): In combination with aspirin in medically treated patients eligible for thrombolytic therapy.
- Prevention of atherothrombotic and thromboembolic events in atrial fibrillation: In adult patients with atrial fibrillation who have at least one risk factor for vascular events, are not suitable for treatment with vitamin K antagonists (VKAs), and have a low bleeding risk. This is typically used when oral anticoagulation is not feasible, though direct oral anticoagulants (DOACs) have largely replaced this indication in current practice.
Mechanism of Action
Clopidogrel is a prodrug that undergoes a two-step hepatic biotransformation. After oral absorption, approximately 85% of the absorbed dose is hydrolysed by esterases to an inactive carboxylic acid metabolite. The remaining 15% is oxidised by hepatic cytochrome P450 enzymes, primarily CYP2C19, with contributions from CYP3A4, CYP2B6, and CYP1A2, to form the pharmacologically active thiol metabolite.
The active metabolite forms a disulphide bridge with the cysteine residue at position 17 and 242 of the P2Y12 receptor on the platelet membrane. This binding is irreversible, meaning that once a platelet has been exposed to the active metabolite, its P2Y12 receptor is permanently blocked for the rest of that platelet's lifespan. Since new platelets are produced continuously by the bone marrow (approximately 10% of the circulating platelet pool is replaced each day), steady-state platelet inhibition with daily dosing is achieved after approximately 3–7 days. A loading dose (300–600 mg) can accelerate this process, achieving significant platelet inhibition within 2–6 hours.
By inhibiting ADP-mediated platelet activation, clopidogrel reduces platelet aggregation, platelet-fibrinogen binding, and the subsequent stabilisation of arterial thrombi at sites of atherosclerotic plaque rupture. This mechanism is complementary to aspirin's inhibition of the thromboxane A2 (TxA2) pathway, which is why the combination of clopidogrel and aspirin (dual antiplatelet therapy) provides more effective antiplatelet protection than either agent alone.
Pharmacokinetics
Clopidogrel is rapidly absorbed after oral administration, with a bioavailability of approximately 50% (the parent compound itself has low bioavailability, but the prodrug is efficiently absorbed). Peak plasma concentrations of the main circulating inactive metabolite (the carboxylic acid derivative) occur approximately 1 hour after dosing. The active thiol metabolite reaches peak concentrations approximately 30–60 minutes after a loading dose. Clopidogrel and its main circulating metabolite bind reversibly to plasma proteins (98% and 94%, respectively). The elimination half-life of the main inactive metabolite is approximately 8 hours. Excretion occurs via both renal (approximately 50%) and faecal (approximately 46%) routes.
What Should You Know Before Taking Clopidogrel Krka d.d.?
Quick Answer: Before starting clopidogrel, your doctor will assess your bleeding risk, liver function, and genetic metaboliser status. Clopidogrel is contraindicated in active pathological bleeding and severe liver disease. CYP2C19 poor metabolisers may need alternative antiplatelet agents. Proton pump inhibitors such as omeprazole should be avoided if possible, as they can reduce clopidogrel effectiveness.
Clopidogrel is a powerful antiplatelet agent that significantly affects your body's ability to form blood clots. While this is the desired therapeutic effect for preventing atherothrombotic events, it also means that careful medical assessment is essential before starting treatment. Your healthcare provider will consider your complete medical history, current medications, and individual risk factors to ensure that clopidogrel is safe and appropriate for you. The decision to prescribe clopidogrel always involves weighing the benefit of preventing ischaemic events against the risk of bleeding.
Contraindications
Clopidogrel should not be used in the following situations:
- Hypersensitivity: Known allergy to clopidogrel or any of the excipients in the formulation. Cross-sensitivity with other thienopyridines (such as ticlopidine) has been reported.
- Active pathological bleeding: Patients with ongoing haemorrhage, such as peptic ulcer bleeding, intracranial haemorrhage, or any other active bleeding site.
- Severe hepatic impairment: Patients with severe liver disease may have increased bleeding risk due to impaired coagulation factor synthesis. Additionally, the hepatic biotransformation required to activate clopidogrel may be compromised.
Clopidogrel is a prodrug that requires conversion to its active form by the liver enzyme CYP2C19. Approximately 2–14% of the population (depending on ethnicity – higher prevalence in East Asian and Pacific Islander populations) carry genetic variants that result in reduced or absent CYP2C19 activity (*2 and *3 alleles). These “poor metabolisers” may not adequately activate clopidogrel, leading to higher residual platelet reactivity and an increased risk of cardiovascular events, particularly stent thrombosis after coronary stent placement. The FDA has issued a boxed warning regarding this issue. Pharmacogenomic testing (CYP2C19 genotyping) can identify these patients, and alternative P2Y12 inhibitors (prasugrel or ticagrelor) that do not depend on CYP2C19 for activation may be recommended.
Warnings and Precautions
Special caution is required when using clopidogrel in the following situations:
- Increased bleeding risk: Patients with conditions that predispose to bleeding (such as recent trauma, surgery, peptic ulcer disease, or haemorrhagic disorders) are at higher risk. Signs and symptoms of bleeding, including occult bleeding from any site, should be monitored. If clopidogrel needs to be discontinued before surgery, it should ideally be stopped 5–7 days prior to allow platelet function recovery.
- Thrombotic thrombocytopenic purpura (TTP): TTP has been reported rarely in association with clopidogrel use, sometimes after a short exposure. It is characterised by thrombocytopenia, microangiopathic haemolytic anaemia, neurological symptoms, renal dysfunction, and fever. TTP is a potentially fatal condition requiring immediate treatment, including plasmapheresis.
- Recent ischaemic stroke: In patients with recent ischaemic stroke, there is limited evidence for the safety of initiating clopidogrel within the first 7 days after the event. Current guidelines generally recommend waiting 7 days before starting clopidogrel monotherapy after ischaemic stroke.
- Renal impairment: Limited experience exists in patients with severe renal impairment. Clopidogrel should be used with caution in these patients.
- Hepatic impairment: Patients with moderate hepatic impairment may have bleeding diathesis. Additionally, exposure to the active metabolite of clopidogrel may be reduced in patients with impaired hepatic function. Clopidogrel should be used with caution in these patients.
- Cross-reactivity with other thienopyridines: Patients with a history of allergic reaction to one thienopyridine (e.g. ticlopidine) may be at increased risk of reaction to another. Alternative antiplatelet agents should be considered.
Pregnancy and Breastfeeding
There are no adequate and well-controlled studies of clopidogrel use during pregnancy in humans. Animal reproduction studies have not revealed evidence of impaired fertility or harm to the foetus at doses up to 500 mg/kg/day in rats and 300 mg/kg/day in rabbits. However, as a precautionary measure, clopidogrel should not be used during pregnancy unless clearly necessary and the potential benefit outweighs the potential risk to the foetus. Women of childbearing potential should discuss contraception with their healthcare provider.
Studies in rats have shown that clopidogrel and/or its metabolites are excreted in breast milk. It is not known whether clopidogrel is excreted in human breast milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breastfeeding or discontinue clopidogrel, taking into account the importance of the drug to the mother.
No dose adjustment is required based on age, gender, or ethnicity. However, elderly patients may be at increased risk of bleeding. Patients with renal impairment do not require dose adjustment, although experience is limited in severe renal impairment. CYP2C19 genotyping should be considered in patients undergoing PCI, particularly those receiving drug-eluting stents, to identify poor metabolisers who may benefit from alternative antiplatelet therapy.
How Does Clopidogrel Krka d.d. Interact with Other Drugs?
Quick Answer: The most clinically significant interaction is with CYP2C19 inhibitors (especially omeprazole and esomeprazole), which reduce clopidogrel activation and antiplatelet effect. Concomitant use with anticoagulants, NSAIDs, and other antiplatelet agents increases bleeding risk. If a proton pump inhibitor is needed, pantoprazole or rabeprazole are preferred alternatives.
Drug interactions with clopidogrel are clinically important because they can either reduce its antiplatelet effectiveness (potentially leading to thrombotic events) or increase the risk of bleeding. The most important interactions involve drugs that affect the CYP2C19 enzyme, which is the primary pathway for clopidogrel's bioactivation, as well as drugs that independently increase bleeding risk. Patients should always inform their healthcare provider about all medications they are taking, including over-the-counter medicines, herbal supplements, and vitamins.
Unlike some other medications, clopidogrel has specific and well-documented pharmacokinetic interactions that can significantly impact clinical outcomes. The interaction between clopidogrel and certain proton pump inhibitors (PPIs) has been one of the most extensively studied drug interactions in cardiovascular medicine, leading to regulatory warnings from both the EMA and FDA.
Major Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Omeprazole, esomeprazole | Strong CYP2C19 inhibitors; reduce formation of clopidogrel active metabolite by approximately 40–50%, significantly reducing antiplatelet effect | Avoid concomitant use. If PPI is needed, use pantoprazole or rabeprazole instead (minimal CYP2C19 inhibition) |
| Oral anticoagulants (warfarin, DOACs) | Additive anticoagulant and antiplatelet effects; markedly increased risk of bleeding | Avoid combination unless specifically indicated (e.g. triple therapy after ACS with AF); if used, shortest duration possible with close monitoring |
| Fluconazole, fluvoxamine, fluoxetine | CYP2C19 inhibitors; may reduce clopidogrel activation and antiplatelet effect | Avoid if possible; consider alternative agents or platelet function testing if concomitant use is necessary |
| Repaglinide | Clopidogrel inhibits CYP2C8; can increase repaglinide exposure (up to 5.1-fold), causing severe and prolonged hypoglycaemia | Avoid concomitant use. Use alternative antiplatelet or antidiabetic agent |
| Thrombolytics (alteplase, tenecteplase) | Markedly increased risk of bleeding when combined with antiplatelet therapy | May be used together in acute STEMI under close medical supervision in hospital setting; monitor carefully for bleeding |
Minor Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| NSAIDs (ibuprofen, naproxen, diclofenac) | Do not alter clopidogrel metabolism but independently increase gastrointestinal bleeding risk | Use with caution; avoid prolonged concomitant use. If analgesia needed, paracetamol (acetaminophen) is preferred |
| Aspirin (acetylsalicylic acid) | Complementary antiplatelet mechanism; intended therapeutic combination (DAPT) but increases bleeding risk | Used together as DAPT when indicated (ACS, post-stent); low-dose aspirin (75–100 mg) preferred; duration as per guidelines |
| SSRIs (sertraline, citalopram, paroxetine) | SSRIs impair platelet serotonin uptake, independently increasing bleeding risk. Some (fluoxetine, fluvoxamine) also inhibit CYP2C19 | Use with caution; choose SSRIs with minimal CYP2C19 inhibition (sertraline, citalopram); monitor for bleeding |
| Pantoprazole, rabeprazole | Weak CYP2C19 inhibitors; minimal effect on clopidogrel active metabolite formation | Preferred PPIs when gastroprotection is needed with clopidogrel |
| Morphine and other opioids | May delay gastric emptying and reduce clopidogrel absorption, delaying onset of antiplatelet effect | Consider IV antiplatelet alternatives (cangrelor) in acute setting if opioids are required; clinical significance debated |
Clopidogrel can be taken with or without food. Food does not significantly affect the absorption or bioactivation of clopidogrel. There are no specific dietary restrictions during clopidogrel therapy. However, grapefruit and grapefruit juice may have a minor inhibitory effect on CYP3A4, which plays a secondary role in clopidogrel metabolism; routine avoidance is not necessary but excessive consumption should be avoided. Alcohol consumption should be moderated as it can increase gastric irritation and bleeding risk.
What Is the Correct Dosage of Clopidogrel Krka d.d.?
Quick Answer: The standard maintenance dose is 75 mg once daily by mouth. For acute coronary syndromes and PCI, a loading dose of 300–600 mg is typically given first for rapid onset of antiplatelet effect. The duration of treatment depends on the clinical indication and can range from 1 month to lifelong therapy.
Clopidogrel dosing is straightforward, using a fixed once-daily dose without the need for blood monitoring or dose titration. However, the initial loading dose and duration of treatment vary depending on the specific clinical indication. It is essential to follow your prescriber's instructions regarding both the dose and the duration of therapy, as premature discontinuation – particularly after coronary stent placement – can have serious and potentially fatal consequences.
Adults
| Indication | Loading Dose | Maintenance Dose | Duration |
|---|---|---|---|
| Recent MI, ischaemic stroke, or established PAD | None required | 75 mg once daily | Long-term (ongoing secondary prevention) |
| NSTE-ACS (with aspirin) | 300 mg single dose | 75 mg once daily (+ aspirin 75–100 mg) | Up to 12 months (minimum 1 month, then reassess) |
| STEMI with thrombolysis (with aspirin) | 300 mg (age ≤75) or no loading dose (age >75) | 75 mg once daily (+ aspirin 75–100 mg) | At least 4 weeks, up to 12 months |
| Post-PCI with drug-eluting stent (DAPT) | 300–600 mg | 75 mg once daily (+ aspirin 75–100 mg) | 6–12 months (may be shortened to 1–3 months in high bleeding risk) |
| Post-PCI with bare-metal stent (DAPT) | 300–600 mg | 75 mg once daily (+ aspirin 75–100 mg) | At least 1 month, typically up to 6 months |
Children
The safety and efficacy of clopidogrel in children and adolescents below 18 years of age have not been established. The CLARINET trial evaluated clopidogrel in neonates and infants with cyanotic congenital heart disease and found no significant benefit over placebo. Current guidelines do not recommend clopidogrel for routine use in paediatric patients. In some paediatric centres, clopidogrel is used off-label for specific indications (such as after Fontan surgery or paediatric stroke), but this should only be done under specialist supervision.
Elderly
No dose adjustment is required for elderly patients. However, elderly patients are at increased risk of bleeding complications and may be more susceptible to the adverse effects of clopidogrel. The benefit-risk balance should be carefully considered, and patients should be monitored for signs and symptoms of bleeding. The CURE trial included patients up to 80 years of age, and the benefits of dual antiplatelet therapy were consistent across age groups, though absolute bleeding risk increased with age.
Missed Dose
What to Do If You Miss a Dose
If you miss a dose of clopidogrel, take it as soon as you remember on the same day. If it is almost time for your next dose, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the missed one. Because clopidogrel irreversibly inhibits platelets, the antiplatelet effect of previously taken doses persists even if a single dose is missed. However, consistent daily dosing is important for maintaining optimal platelet inhibition, so try to take your medication at the same time each day.
Overdose
Overdose with clopidogrel may lead to prolonged bleeding time and subsequent bleeding complications. There is no specific antidote for clopidogrel. If rapid correction of prolonged bleeding time is required, a platelet transfusion may reverse the effects of clopidogrel, as it provides fresh platelets with uninhibited P2Y12 receptors. In case of suspected overdose, contact your local poison control centre or seek emergency medical attention immediately. Supportive measures and symptomatic treatment should be provided as appropriate.
What Are the Side Effects of Clopidogrel Krka d.d.?
Quick Answer: The most common side effects of clopidogrel are bleeding (including bruising, nosebleeds, and gastrointestinal bleeding), gastrointestinal symptoms (dyspepsia, abdominal pain, diarrhoea), and haematoma. Serious but rare side effects include thrombotic thrombocytopenic purpura (TTP), severe haemorrhage, and hepatic disorders. Most patients tolerate clopidogrel well.
Like all medicines, clopidogrel can cause side effects, although not everybody gets them. The most important and most common side effect is bleeding, which is a direct consequence of the drug's antiplatelet mechanism of action. The risk of bleeding is increased when clopidogrel is used in combination with aspirin (dual antiplatelet therapy) or with other medicines that affect blood clotting. Most bleeding events are mild (such as bruising or minor nosebleeds), but serious and occasionally life-threatening bleeding can occur.
The side effect profile of clopidogrel has been well characterised through large clinical trials involving tens of thousands of patients, as well as decades of post-marketing surveillance. The following frequencies are based on data from the CAPRIE, CURE, and CLARITY-TIMI 28 clinical trials, as well as post-marketing reports compiled in the EMA-approved SmPC.
It is important to report any unusual symptoms to your healthcare provider, particularly signs of bleeding (unexpected bruising, blood in urine or stools, prolonged bleeding from cuts, coughing up blood), skin reactions, or signs of liver problems (yellowing of the skin or eyes, dark urine, abdominal pain).
Common
May affect up to 1 in 10 people
- Haematoma (bruising)
- Epistaxis (nosebleeds)
- Gastrointestinal haemorrhage (bleeding in the stomach or intestines)
- Diarrhoea
- Abdominal pain
- Dyspepsia (indigestion)
Uncommon
May affect up to 1 in 100 people
- Thrombocytopenia (low platelet count)
- Leucopenia (low white blood cell count)
- Eosinophilia (elevated eosinophils)
- Intracranial haemorrhage (bleeding in the brain)
- Headache, dizziness, paraesthesia
- Gastric ulcer, duodenal ulcer
- Gastritis, vomiting, nausea, constipation, flatulence
- Rash, pruritus (itching)
- Haematuria (blood in urine)
- Bleeding at puncture site
- Prolonged bleeding time
Rare
May affect up to 1 in 1,000 people
- Neutropenia (severe low white blood cell count)
- Retroperitoneal haemorrhage
- Severe gastrointestinal haemorrhage
- Hepatitis, abnormal liver function tests
- Arthralgia (joint pain), myalgia (muscle pain)
- Glomerulonephritis (kidney inflammation)
- Fever
Very Rare
May affect up to 1 in 10,000 people
- Thrombotic thrombocytopenic purpura (TTP)
- Aplastic anaemia, pancytopenia, agranulocytosis
- Severe thrombocytopenia (platelet count <30 × 10⁹/L)
- Serum sickness
- Anaphylactoid reactions
- Confusion, hallucinations
- Taste disturbances (ageusia)
- Severe hepatic failure, acute liver failure
- Vasculitis, hypotension
- Interstitial pneumonitis, eosinophilic pneumonia
- Stomatitis
- Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
- Angioedema
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Acquired haemophilia A
Contact your doctor or seek emergency medical help immediately if you experience: severe or uncontrolled bleeding from any site; black, tarry stools or blood in your stools; vomiting blood or material that looks like coffee grounds; unexplained severe headache with sudden onset; signs of stroke (sudden weakness, confusion, speech difficulty, vision problems); severe skin reactions (widespread rash, blistering, peeling); jaundice (yellowing of skin or eyes); or signs of severe allergic reaction (swelling of face, throat, or difficulty breathing).
How Should You Store Clopidogrel Krka d.d.?
Quick Answer: Store Clopidogrel Krka d.d. at room temperature below 25°C (77°F), in the original packaging to protect from moisture and light. Keep out of the reach and sight of children. Do not use after the expiry date stated on the packaging.
Proper storage of medicines is important to ensure they remain effective and safe throughout their shelf life. Clopidogrel Krka d.d. film-coated tablets should be stored under the following conditions:
- Temperature: Store below 25°C (77°F). Do not refrigerate or freeze.
- Moisture protection: Keep the tablets in the original blister packaging until ready to use. The aluminium foil blister provides protection from moisture, which could otherwise degrade the tablet coating.
- Light protection: Store in the original outer carton to protect from light exposure.
- Accessibility: Keep out of the reach and sight of children. Use child-resistant packaging where available.
- Expiry date: Do not use the tablets after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment. If you notice any visible changes to the tablets (discolouration, crumbling, unusual odour), do not use them and consult your pharmacist.
What Does Clopidogrel Krka d.d. Contain?
Quick Answer: Each film-coated tablet contains 75 mg of clopidogrel (as clopidogrel hydrogen sulphate) as the active ingredient. The tablets also contain various inactive excipients used in the tablet core and film coating to ensure stability, absorption, and ease of swallowing.
Understanding the full composition of your medicine is important, particularly if you have known allergies or intolerances to specific excipients. The complete composition of Clopidogrel Krka d.d. 75 mg film-coated tablets is as follows:
Active Ingredient
Each film-coated tablet contains clopidogrel hydrogen sulphate equivalent to 75 mg of clopidogrel base. Clopidogrel hydrogen sulphate is a white to off-white crystalline powder with the molecular formula C₁₆H₁₆ClNO₂S · H₂SO₄ and a molecular weight of 419.9 g/mol. The INN (International Non-proprietary Name) is clopidogrel.
Inactive Ingredients (Excipients)
The excipients used in Clopidogrel Krka d.d. tablets are standard pharmaceutical-grade ingredients commonly used in oral solid dosage forms. The tablet core typically contains:
- Microcrystalline cellulose – filler/diluent and binder
- Hydroxypropylcellulose (low-substituted) – disintegrant
- Maize starch, pregelatinised – binder and disintegrant
- Macrogol 6000 – lubricant/processing aid
- Hydrogenated castor oil – lubricant
The film coating (Opadry II Pink) typically contains:
- Hypromellose (HPMC) – film-forming polymer
- Titanium dioxide (E171) – opacifier and colourant
- Macrogol 6000 – plasticiser
- Talc – anti-tack agent
- Iron oxide red (E172) – colourant
The film-coated tablets are round, biconvex, pink-coloured, debossed with “75” on one side and plain on the other. The film coating provides protection from moisture and stomach acid, ensures a smooth surface for ease of swallowing, and masks any unpleasant taste of the active ingredient.
Clopidogrel Krka d.d. tablets do not contain lactose, gluten, or sucrose. However, patients with known hypersensitivity to any of the listed excipients should not take this medicine. If you are unsure about any ingredients, consult your pharmacist or healthcare provider before taking the medication.
Frequently Asked Questions About Clopidogrel Krka d.d.
Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients with atherosclerotic cardiovascular disease. It is prescribed after heart attacks (myocardial infarction), ischaemic strokes, and in patients with peripheral arterial disease. It is also used in combination with aspirin (dual antiplatelet therapy) after coronary stent placement and in acute coronary syndromes to reduce the risk of further cardiovascular events. Clopidogrel Krka d.d. is a generic version containing the same active ingredient as the original brand Plavix.
Omeprazole and esomeprazole are CYP2C19 inhibitors that can reduce the effectiveness of clopidogrel by decreasing formation of its active metabolite. Both the EMA and FDA advise avoiding this combination. If you need a proton pump inhibitor for stomach protection (which is sometimes needed during dual antiplatelet therapy), pantoprazole or rabeprazole are preferred alternatives as they have minimal effect on CYP2C19. Alternatively, H2 receptor antagonists (such as ranitidine or famotidine) may be used.
After coronary stent placement, dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is typically recommended for 6–12 months for drug-eluting stents and at least 1 month for bare-metal stents. The exact duration depends on your individual risk factors for both clotting (ischaemic risk) and bleeding. Some patients at high ischaemic risk may benefit from longer DAPT, while those at high bleeding risk may be considered for shorter DAPT (1–3 months). This decision should be made by your cardiologist based on your specific clinical situation.
Clopidogrel is a prodrug that must be converted to its active form by the liver enzyme CYP2C19. Approximately 2–14% of the population carry genetic variants (*2 and *3 alleles) that reduce CYP2C19 activity. These “poor metabolisers” may not adequately activate clopidogrel, leading to reduced antiplatelet effect and higher risk of cardiovascular events, particularly stent thrombosis. Pharmacogenomic testing can identify these patients. If you are a poor metaboliser, your doctor may recommend alternative P2Y12 inhibitors such as prasugrel or ticagrelor, which do not depend on CYP2C19 for activation.
Clopidogrel Krka d.d. is a generic version that contains the same active ingredient (clopidogrel hydrogen sulphate) at the same dose (75 mg) as the original brand Plavix. Generic medicines approved by the EMA must demonstrate bioequivalence, meaning they deliver the same amount of active ingredient at the same rate as the originator product. The excipients (inactive ingredients) may differ slightly, but this does not affect the clinical efficacy or safety of the medicine. The main advantage of generic versions is typically lower cost.
If you miss a dose, take it as soon as you remember on the same day. If it is almost time for your next dose, skip the missed dose and continue with your normal schedule. Do not take a double dose. Because clopidogrel irreversibly inhibits platelets, a single missed dose is unlikely to cause immediate problems, as platelets already inhibited will remain so. However, consistent daily dosing is important for maintaining optimal antiplatelet protection, so try to take your tablet at the same time each day.
Clopidogrel should generally be discontinued 5–7 days before elective surgery to allow platelet function to recover. However, for patients with recent coronary stents, stopping clopidogrel prematurely is dangerous due to the risk of stent thrombosis, which can be fatal. The decision to stop clopidogrel before surgery should always be made by your doctor, ideally in consultation with your cardiologist, carefully weighing the surgical bleeding risk against the risk of thrombotic events. For urgent surgery, platelet transfusion can be considered to reverse the antiplatelet effect.
References and Sources
- Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation (CURE trial). New England Journal of Medicine. 2001;345(7):494-502. doi:10.1056/NEJMoa010746
- CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348(9038):1329-1339. doi:10.1016/S0140-6736(96)09457-3
- Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation (CLARITY-TIMI 28). New England Journal of Medicine. 2005;352(12):1179-1189. doi:10.1056/NEJMoa050522
- Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. European Heart Journal. 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191
- Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. Journal of the American College of Cardiology. 2016;68(10):1082-1115.
- Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clinical Pharmacology & Therapeutics. 2013;94(3):317-323.
- European Medicines Agency (EMA). Summary of Product Characteristics – Clopidogrel. Last updated 2024.
- U.S. Food and Drug Administration (FDA). Clopidogrel (Plavix) – FDA Label and Boxed Warning. Updated 2023.
- British National Formulary (BNF). Clopidogrel. National Institute for Health and Care Excellence (NICE). Updated 2025.
- World Health Organization (WHO). Model List of Essential Medicines – 23rd List (2023). Clopidogrel is listed as an essential antiplatelet agent.
Editorial Team
iMedic Medical Editorial Team – specialists in clinical pharmacology, cardiology, and internal medicine. Our team includes licensed physicians with clinical experience in antiplatelet therapy and cardiovascular disease management.
iMedic Medical Review Board – an independent panel of medical experts who verify all content according to international guidelines (ESC, AHA/ACC, EMA, FDA, WHO). All medical claims are evidence-based with Level 1A evidence from systematic reviews and randomised controlled trials.
All medical content on iMedic is written and reviewed by qualified healthcare professionals. We follow the GRADE evidence framework and cite only peer-reviewed sources and established medical guidelines. Our content is free from commercial influence – we receive no funding from pharmaceutical companies. For more information, visit our editorial standards page.