Platz

Each film-coated tablet contains Clopidogrel hydrogen sulphate 97.875 mg (molar equivalent of Platz base 75 mg) or Platz hydrogen sulphate 391.5 mg (molar equivalent of Platz base 300 mg).

Platz also contains the following excipients: Hydrogenated castor oil, hydroxypropyl cellulose, mannitol E421, microcrystalline cellulose and polyethylene glycol 6000 as inactive ingredient. The pink film coating contains ferric oxide E172, hypromellose 2910, lactose, titanium dioxide and triacetin. The tablets are polished with carnauba wax.

Platz hydrogen sulfate is methyl(+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1). It has an empirical formula of C₁₆H₁₆CINO₂S·H₂SO₄ and a molecular weight of 419.9.

Platz hydrogen sulfate is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex.

Platz hydrogen sulfate is a white to off-white powder. It is practically insoluble in water at neutral pH but freely soluble at pH 1. It also dissolves freely in methanol, dissolves slightly in methylene chloride, and is practically insoluble in ethyl ether. It has a specific optical rotation of about +56°.

Prevention of atherothrombotic events in: Recent MI, Recent Stroke or Established Peripheral Arterial Disease: For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Platz has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.

Acute Coronary Syndrome: For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or coronary artery bypass graft (CABG), Platz has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke or refractory ischemia.

For patients with ST-segment elevation acute MI, Platz has been shown to reduce the rate of death from any cause and the rate of a combined endpoint of death, reinfarction or stroke.

Atrial Fibrillation: In patients with atrial fibrillation (AF) at increased risk of vascular events who can take vitamin K antagonist (VKA) therapy, VKA has been shown to be associated with a better clinical benefit than acetylsalicylic acid (aspirin) alone or the combination of Platz and aspirin for the reduction of stroke.

In patients with atrial fibrillation who have at least 1 risk factor for vascular events and who cannot take VKA therapy [eg, specific risk of bleeding, physician assessment that patient is unable to comply with international normalized ratio (INR) monitoring or that VKA use is inappropriate], Platz is indicated in combination with aspirin for the prevention of atherothrombotic and thromboembolic events, including stroke. Platz in combination with aspirin has been shown to reduce the rate of the combined endpoint of stroke, myocardial infarction (MI), non-CNS systemic embolism, or vascular death, largely through a reduction in stroke.

Platz is used alone or together with aspirin to lessen the chance of a heart attack or stroke. It is given to patients who have already had a heart attack, severe chest pain, or a stroke, or to patients with other circulation problems that could cause a stroke or heart attack.

A heart attack or stroke may occur when a blood vessel is blocked by a blood clot. Platz is a platelet inhibitor. It reduces the chance that a harmful blood clot will form by preventing platelets from clumping together in the blood. Platz may also increase the chance of serious bleeding in some people.

Platz is available only with your doctor's prescription.

Acute Coronary Syndrome

Platz can be administered with or without food.

• For patients with non-ST-elevation ACS (UA/NSTEMI), initiate Platz with a single 300 mg oral loading dose and then continue at 75 mg once daily. Initiate aspirin (75-325 mg once daily) and continue in combination with Platz.
• For patients with STEMI, the recommended dose of Platz is 75 mg once daily orally, administered in combination with aspirin (75-325 mg once daily), with or without thrombolytics. Platz may be initiated with or without a loading dose.

Recent MI, Recent Stroke, Or Established Peripheral Arterial Disease

The recommended daily dose of Platz is 75 mg once daily orally, with or without food.

CYP2C19 Poor Metabolizers

CYP2C19 poor metabolizer status is associated with diminished antiplatelet response to Platz. Although a higher dose regimen in poor metabolizers increases antiplatelet response, an appropriate dose regimen for this patient population has not been established.

Use With Proton Pump Inhibitors (PPI)

Avoid using omeprazole or esomeprazole with Platz. Omeprazole and esomeprazole significantly reduce the antiplatelet activity of Platz. When concomitant administration of a PPI is required, consider using another acid-reducing agent with minimal or no CYP2C19 inhibitory effect on the formation of Platz active metabolite.

How supplied

Dosage Forms And Strengths

• 75 mg tablets: Pink, round, biconvex, film-coated tablets debossed with “75” on one side and “1171” on the other
• 300 mg tablets: Pink, oblong, film-coated tablets debossed with “300” on one side and “1332” on the other

Storage And Handling

Platz (Platz bisulfate) 75 mg tablets are available as pink, round, biconvex, film-coated tablets debossed with “75” on one side and “1171” on the other. Tablets are provided as follows:

NDC 63653-1171-6 Bottles of 30

NDC 63653-1171-1 Bottles of 90

NDC 63653-1171-5 Bottles of 500

NDC 63653-1171-3 Blisters of 100

Platz (Platz bisulfate) 300 mg tablets are available as pink, oblong, film-coated tablets debossed with “300” on one side and “1332” on the other. Tablets are provided as follows:

NDC 63653-1332-2 Unit-dose packages of 30

NDC 63653-1332-3 Unit-dose packages of 100

Store at 25° C (77° F); excursions permitted to 15°–30° C (59°–86° F).

Distributed by: Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Bridgewater, NJ 08807. Revised: July 2015

See also:
What is the most important information I should know about Platz?

Platz should not be used whenever stimulation of gastrointestinal motility might be dangerous, e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation.

Platz is contraindicated in patients with pheochro-mocytoma because the drug may cause a hypertensive crisis, probably due to release of catecholamines from the tumor. Such hypertensive crises may be controlled by phen-tolamine.

Platz is contraindicated in patients with known sensitivity or intolerance to the drug.

Platz should not be used in epileptics or patients receiving other drugs which are likely to cause extrapyramidal reactions, since the frequency and severity of seizures or extrapyramidal reactions may be increased.

Use Platz as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Platz by mouth with or without food.
• Take Platz on a regular schedule to get the most benefit from it.
• Do not stop taking Platz without talking to your doctor. This may increase the risk of heart problems.
• If you miss a dose of Platz, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Platz.

Use: Labeled Indications

Acute coronary syndrome:

ST-segment elevation myocardial infarction: To reduce the rate of myocardial infarction (MI) and stroke in conjunction with aspirin in patients with acute ST-elevation MI who are to be managed medically.

Non-ST-segment elevation acute coronary syndromes: To decrease the rate of MI and stroke in conjunction with aspirin in patients with non-ST-segment elevation acute coronary syndromes (unstable angina/non-ST-elevation MI), including patients who are to be managed medically and those who are to be managed with coronary revascularization.

Myocardial infarction, ischemic stroke, or peripheral atherosclerotic disease: To reduce the rate of MI and stroke in patients with a history of recent MI, recent stroke, or established peripheral atherosclerotic disease.

Off Label Uses

Carotid artery atherosclerosis, symptomatic

Based on the American College of Chest Physicians guidelines for antithrombotic therapy in peripheral artery disease, Platz is effective and recommended for patients with symptomatic carotid artery atherosclerosis.

Carotid artery stenting

A randomized, controlled trial with blinded end point adjudication evaluated carotid artery stenting versus carotid endarterectomy in patients with carotid artery stenosis. In this trial, aspirin in combination with Platz was used for patients who underwent carotid artery stenting, which suggests that this antiplatelet combination is effective.

See also:
What other drugs will affect Platz?

Oral Anticoagulants:

Glycoprotein IIb/IIIa Inhibitors: As a pharmacodynamic interaction between Platz and glycoprotein IIb/IIIa inhibitors is possible, concomitant use should be undertaken with caution.

Acetylsalicylic Acid: Acetylsalicylic acid did not modify the Platz-mediated inhibition of ADP-induced platelet aggregation, but Platz potentiated the effect of ASA on collagen-induced platelet aggregation. However, concomitant administration of ASA 500 mg twice daily for 1 day did not significantly increase the prolongation of bleeding time induced by Platz intake. As a pharmacodynamic interaction between Platz and ASA is possible, leading to increased risk of bleeding. Therefore, concomitant use should be undertaken with caution. However, Platz and ASA have been administered together for up to 1 year.

Injectable Anticoagulants: In a clinical study conducted in healthy subjects, Platz did not necessitate modification of the heparin dose or alter the effect of heparin on coagulation. Co-administration of heparin had no effect on the IPA induced by Platz. As a pharmacodynamic interaction between Platz and heparin is possible, concomitant use should be undertaken with caution.

Thrombolytics: The safety of the concomitant administration of Platz, thrombolytic agents and heparins was assessed in patients with acute MI. The incidence of clinically significant bleeding was similar to that observed when thrombolytic agents and heparins are co-administered with ASA.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In a clinical study conducted in healthy volunteers, the concomitant administration of Platz and naproxen increased occult gastrointestinal blood loss. However, due to the lack of interaction studies with other NSAIDs, it is presently unclear whether there is an increased risk of gastrointestinal bleeding with all NSAIDs. Consequently, NSAIDs including COX-2 inhibitors and Platz should be co-administered with caution.

Selective Serotonin Reuptake Inhibitors (SSRIs): Since SSRIs affect platelet activation and increase the risk of bleeding, the concomitant administration of SSRIs with Platz should be undertaken with caution.

Other Concomitant Therapy: Since Platz is metabolised to its active metabolite partly by CYP2C19, use of drugs that inhibit the activity of this enzyme would be expected to result in reduced drug levels of the active metabolite of Platz. The clinical relevance of this interaction is uncertain. Concomitant use of strong or moderate CYP2C19 inhibitors (eg, omeprazole) should be discouraged. If a proton-pump inhibitor is to be used concomitantly with Platz, consider using one with less CYP2C19 inhibitory activity eg, pantoprazole.

Proton-Pump Inhibitors (PPI): In a crossover clinical study, Platz (300-mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg at the same time as Platz) were administered for 5 days. The exposure to the active metabolite of Platz was decreased by 45% (day 1) and 40% (day 5) when Platz and omeprazole were administered together. Mean IPA with 5 mM ADP was diminished by 39% (24 hrs) and 21% (day 5) when Platz and omeprazole were administered together.

In a 2nd interaction study with omeprazole 80 mg administered 12 hrs apart from the Platz standard regimen, the results were similar, indicating that administering Platz and omeprazole at different times does not prevent their interaction that is likely to be driven by the inhibitory effect of omeprazole on CYP2C19.

In a 3rd interaction study with omeprazole 80 mg administered with a higher dose regimen of Platz (600-mg loading dose followed by 150 mg/day), a degree of interaction was observed similar to that noted in the other omeprazole interaction studies. However, active metabolite formation and platelet aggregation were at the same level as Platz administered alone at the standard dose regimen.

In a crossover clinical study, healthy subjects were administered Platz (300-mg loading dose followed by 75 mg/day) alone and with pantoprazole (80 mg at the same time as Platz) for 5 days. The exposure to the active metabolite of Platz was decreased by 20% (day 1) and 14% (day 5) when Platz and pantoprazole were administered together. Mean IPA was diminished by 15% (24 hrs) and 11% (day 5) when Platz and pantoprazole were administered together. These results indicate that Platz can be administered with pantoprazole.

The CURRENT trial compared 2 dosing regimens of Platz (600-mg loading dose, then 150 mg/day for 6 days followed by 75 mg/day up to 30 days vs 300-mg loading dose followed by 75 mg/day up to 30 days). A subanalysis (n=18,432) correlated PPI use (mainly omeprazole and pantoprazole) at randomization and hospital discharge and demonstrated no interaction between Platz and PPI use for the primary endpoint (CV death, MI or stroke) or any secondary endpoints, including stent thrombosis.

A number of other clinical studies have been conducted with Platz and other concomitant medications to investigate the potential for pharmacodynamic and pharmacokinetic interactions. No clinically significant pharmacodynamic interactions were observed when Platz was co-administered with atenolol, nifedipine or both atenolol and nifedipine. Furthermore, the pharmacodynamic activity of Platz was not significantly influenced by the co-administration of phenobarbital, or oestrogen.

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of Platz. Antacids did not modify the extent of Platz absorption.

Although the administration of Platz 75 mg/day did not modify the pharmacokinetics of S-warfarin (a CYP2C9 substrate) or INR in patients receiving long-term warfarin therapy, co-administration of Platz with warfarin increases the risk of bleeding because of independent effects on hemostasis. However, at high concentrations in vitro, Platz inhibits CYP2C9. It is unlikely that Platz may interfere with the metabolism of drugs eg, phenytoin and tolbutamide and the NSAIDs, which are metabolised by cytochrome P-450 2C9. Data from the CAPRIE study indicate that phenytoin and tolbutamide can be safely co-administered with Platz.

Apart from the specific drug interaction information described previously, interaction studies with Platz and some drugs commonly administered in patients with atherothrombotic disease have not been performed. However, patients entered into clinical trials with Platz received a variety of concomitant medications including diuretics, β-blockers, ACE inhibitors, calcium antagonists, cholesterol lowering agents, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic agents, hormone replacement therapy and GP IIb/IIIa antagonists without evidence of clinically significant adverse interactions.

Incompatibilities: Not applicable.

See also:
What are the possible side effects of Platz?

Platz has been evaluated for safety in more than 44,000 patients who have participated in clinical studies, including >12,000 patients treated for ≥1 year. Overall, Platz 75 mg/day was comparable to ASA 325 mg/day in CAPRIE regardless of age, gender and race. The clinically relevant adverse reactions observed in the CAPRIE, CURE, CLARITY, COMMIT and ACTIVE-A studies are discussed as follows. In addition to clinical studies experience, adverse reactions have been spontaneously reported.

Bleeding is the most common reaction reported both in clinical studies as well as in post-marketing experience where it was mostly reported during the 1st month of treatment.

In CAPRIE, in patients treated with either Platz or ASA, the overall incidence of any bleeding was 9.3%. The incidence of severe cases was similar for Platz and ASA.

In CURE, there was no excess in major bleeds with Platz + ASA within 7 days after coronary bypass graft surgery in patients who stopped therapy >5 days prior to surgery. In patients who remained on therapy within 5 days of bypass graft surgery, the event rate was 9.6% for Platz + ASA, and 6.3% for placebo + ASA.

In CLARITY, there was an overall increase in bleeding in the Platz + ASA group versus the placebo + ASA group. The incidence of major bleeding was similar between groups. This was consistent across subgroups of patients defined by baseline characteristics, and type of fibrinolytic or heparin therapy.

In COMMIT, the overall rate of noncerebral major bleeding or cerebral bleeding was low and similar in both groups.

In ACTIVE-A, the rate of major bleeding was greater in the Platz + ASA group than in the placebo + ASA group (6.7% vs 4.3%). Major bleeding was mostly of extracranial origin in both groups (5.3% in the Platz + ASA group; 3.5% in the placebo + ASA group), mainly from the gastrointestinal tract (3.5% vs 1.8%). There was an excess of intracranial bleeding in the Platz + ASA treatment group compared to the placebo + ASA group (1.4% vs 0.8%, respectively). There was no statistically significant difference in the rates of fatal bleeding (1.1% in the Platz + ASA group and 0.7% in the placebo + ASA group) and haemorrhagic stroke (0.8% and 0.6%, respectively) between groups.

Adverse reactions that occurred either during clinical studies or that were spontaneously reported are presented in Table 2. Their frequency is defined using the following conventions: Common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000). Within each system organ class, adverse reactions are presented in order of decreasing seriousness.