Pletal

Name: Pletal

Pletal Interactions

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • warfarin (Coumadin)
  • aspirin
  • antifungal medications such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and posaconazole (Noxafil)
  • antiplatelet medications such as clopidogrel (Plavix), prasugrel (Effient), and ticlopidine (Ticlid)
  • clarithromycin (Biaxin)
  • diltiazem (Cardizem, Dilacor, Tiazac, and others)
  • erythromycin (E-mycin, Ery-Tab, and others)
  • fluoxetine (Prozac)
  • fluvoxamine (Luvox)
  • nefazodone
  • omeprazole (Prilosec)
  • sertraline (Zoloft)

This is not a complete list of Pletal drug interactions. Ask your doctor or pharmacist for more information.

Pletal Precautions

Serious side effects have been reported with Pletal including the following:

  • fast or irregular heartbeat
  • unusual bleeding or bruising
  • swelling of the arms, hand, feet, ankles, or lower legs

Pletal can cause dizziness. Do not drive or operate heavy machinery until you know how this medication affects you.

Do not take Pletal if you:

  • are allergic to Pletal or to any of its ingredients
  • have congestive heart failure
  • have bleeding disorders or active bleeding, such as bleeding ulcers, bleeding in the brain, or bleeding from any other part of the body
  • have a low platelet count

What should I discuss with my healthcare provider before taking Pletal (cilostazol)?

Do not take cilostazol if you have congestive heart failure. Cilostazol can make this condition worse.

To make sure cilostazol is safe for you, tell your doctor if you have:

  • liver or kidney disease;

  • heart disease; or

  • if you smoke.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether cilostazol passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

What should I avoid while taking Pletal (cilostazol)?

Grapefruit and grapefruit juice may interact with cilostazol and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

Introduction

Platelet-aggregation inhibitor and arterial vasodilator.1 7 8

Pletal Pharmacokinetics

Absorption

Bioavailability

Absorbed following oral administration; bioavailability not determined.1

Onset

Peak pharmacodynamic effects (antiplatelet activity, heart-rate increase, decrease in DBP) within approximately 6 hours.25 In intermittent claudication, symptomatic relief may occur within 2–4 weeks of initial therapy; ≤12 weeks may be required to obtain optimum therapeutic effect.1 2 3 4

Food

Food increases absorption; approximately 90% increase in peak plasma concentration and 25% increase in AUC when administered with a high-fat meal.1 13 18

Increased plasma concentrations may be associated with a higher incidence of adverse effects;13 drug should be taken on an empty stomach.1 13 (See Oral Administration under Dosage and Administration.)

Concomitant ingestion of grapefruit juice increased peak plasma cilostazol concentrations by approximately 50% but had no effect on AUC.1 13

Distribution

Extent

Distributed into milk in rats; not known whether crosses placenta or distributes into milk in humans.1

Plasma Protein Binding

95–98% (mainly albumin).1

Special Populations

In patients with severe renal impairment, metabolite levels increase, and protein binding of drug and metabolites altered; overall drug activity appears unchanged.1

In patients who smoke, drug exposure decreases by approximately 20%.1

Elimination

Metabolism

Metabolized to active metabolites in the liver by CYP isoenzymes, principally CYP3A4, and to lesser extent, by CYP2C19.1 2 17 Two metabolites are active; one metabolite accounts for ≥50% of pharmacologic activity (PDE inhibition).1

Elimination Route

Excreted principally in urine (74%) and also in feces (20%) as active and inactive metabolites.1

Unlikely to be removed by hemodialysis because of high (95–98%) protein binding.1

Half-life

Approximately 11–13 hours (drug and active metabolites).1

What are some other side effects of Pletal?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Dizziness.
  • Headache.
  • Loose stools (diarrhea).
  • Stools that are not normal.
  • Upset stomach.
  • Nose or throat irritation.
  • Belly pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Pletal or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Pletal. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Pletal Dosage and Administration

Recommended dosage

The recommended dosage of Pletal is 100 mg twice daily taken at least half an hour before or two hours after breakfast and dinner.

Patients may respond as early as 2 to 4 weeks after the initiation of therapy, but treatment for up to 12 weeks may be needed before a beneficial effect is experienced. If symptoms are unimproved after 3 months, discontinue Pletal.

Dose Reduction with CYP3A4 and CYP2C19 Inhibitors

Reduce dose to 50 mg twice daily when coadministered with strong or moderate inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, erythromycin, and diltiazem) or inhibitors of CYP2C19 (e.g., ticlopidine, fluconazole, and omeprazole)[see Drug Interactions (7.1)]

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information)

Advise the patient:

• to take Pletal at least one-half hour before or two hours after food. • to discuss with their doctor before taking any CYP3A4 or CYP2C19 inhibitors (e.g., omeprazole). • that the beneficial effects of Pletal on the symptoms of intermittent claudication may not be immediate. Although the patient may experience benefit in 2 to 4 weeks after initiation of therapy, treatment for up to 12 weeks may be required before a beneficial effect is experienced. Discontinue Pletal if symptoms do not improve after 3 months.

Manufactured for

OTSUKA AMERICA PHARMACEUTICAL, INC.

Rockville, MD 20850

Manufactured by

OTSUKA PHARMACEUTICAL CO., LTD.

Tokushima 771-0182, Japan

May 2017

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