Pletal
Encyclopedia
Cilostazol is a medication
used in the alleviation of the symptom
of intermittent claudication
in individuals with peripheral vascular disease. It is manufactured by Otsuka Pharmaceutical Co.
under the trade name
Pletal.
Although drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure
, studies of significant size have not addressed people without the disease.
Cilostazol is a phosphodiesterase inhibitor
with therapeutic focus on cAMP
. It inhibits platelet aggregation and is a direct arterial vasodilator. Its main effects are dilation of the arteries
supplying blood
to the legs and decreasing platelet
coagulation
.
) with therapeutic focus on increasing cAMP
. An increase in cAMP results in an increase in the active form of PKA, which is directly related with an inhibition in platelet aggregation.
. The typical dose is 100 mg twice a day. The effects may take as long as 3 months to be evident and has been shown to improve pain-free walking distance by 50%.
(the most common), diarrhea
, abnormal stool
s, increased heart rate
, and palpitations.
and CYP2C19
, two isoenzymes of the cytochrome P450 system. Drugs that inhibit
CYP3A4, such as itraconazole
, erythromycin
, ketoconazole
, and diltiazem
, are known to interact
with cilostazol. The proton pump inhibitor
omeprazole
, a potent inhibitor of CYP2C19, increases exposure to the active metabolite
of cilostazol.
There has been a single report of grapefruit juice
possibly increasing the effects of cilostazol; some drug information sources list this as a possible interaction. The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's maximum concentration
by around 50%.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used in the alleviation of the symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
of intermittent claudication
Intermittent claudication
Intermittent claudication is a clinical diagnosis given for muscle pain , classically in the calf muscle, which occurs during exercise, such as walking, and is relieved by a short period of rest.Claudication derives from the Latin verb claudicare, "to limp".-Signs:One of the hallmarks of arterial...
in individuals with peripheral vascular disease. It is manufactured by Otsuka Pharmaceutical Co.
Otsuka Pharmaceutical Co.
, abbreviated OPC, is a pharmaceutical company headquartered in Tokyo, Osaka and Naruto, Japan. The company was established August 10, 1964, and currently has approximately 27,000 employees worldwide. The company focuses on pharmaceuticals related to nutrition...
under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Pletal.
Although drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, studies of significant size have not addressed people without the disease.
Cilostazol is a phosphodiesterase inhibitor
Phosphodiesterase inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE...
with therapeutic focus on cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
. It inhibits platelet aggregation and is a direct arterial vasodilator. Its main effects are dilation of the arteries
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
supplying blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
to the legs and decreasing platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
.
Mechanism
Cilostazol is a selective inhibitor of 3-type phosphodiesterase (PDE3PDE3
PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism....
) with therapeutic focus on increasing cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
. An increase in cAMP results in an increase in the active form of PKA, which is directly related with an inhibition in platelet aggregation.
Clinical use
Cilostazol is approved for the treatment of intermittent claudicationIntermittent claudication
Intermittent claudication is a clinical diagnosis given for muscle pain , classically in the calf muscle, which occurs during exercise, such as walking, and is relieved by a short period of rest.Claudication derives from the Latin verb claudicare, "to limp".-Signs:One of the hallmarks of arterial...
. The typical dose is 100 mg twice a day. The effects may take as long as 3 months to be evident and has been shown to improve pain-free walking distance by 50%.
In people with heart failure
Cilostazol, clearly effective for a debilitating condition whose current treatment is often inadequate, is a member of a pharmacologic class that is dangerous to people with severe heart failure and unstudied in other people. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine that there is no risk at all. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available.Adverse effects
Possible side effects of cilostazol use include headacheHeadache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
(the most common), diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, abnormal stool
Human feces
Human feces , also known as a stool, is the waste product of the human digestive system including bacteria. It varies significantly in appearance, according to the state of the digestive system, diet and general health....
s, increased heart rate
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, and palpitations.
Interactions
Cilostazol is metabolized by CYP3A4CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
and CYP2C19
CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...
, two isoenzymes of the cytochrome P450 system. Drugs that inhibit
Enzyme induction and inhibition
Enzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...
CYP3A4, such as itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
, erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
, ketoconazole
Ketoconazole
Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
, and diltiazem
Diltiazem
Diltiazem is a non-dihydropyridine member of the class of drugs known as calcium channel blockers, used in the treatment of hypertension, angina pectoris, and some types of arrhythmia....
, are known to interact
Drug interaction
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind...
with cilostazol. The proton pump inhibitor
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
, a potent inhibitor of CYP2C19, increases exposure to the active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of cilostazol.
There has been a single report of grapefruit juice
Grapefruit juice
Grapefruit juice is the fruit juice from grapefruits. It is rich in Vitamin C and ranges from sweet-tart to very sour. It is considered by some cultures to be a mystical tonic which promotes health and vigor. Certain civilizations have had holy men who live on Grapefruit juice alone...
possibly increasing the effects of cilostazol; some drug information sources list this as a possible interaction. The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's maximum concentration
Cmax
cmax may refer to:* Customatix, a footwear company* C Max, a maximum security prison in South Africa* Ford C-MAX, a model of car* Cmax - the maximum concentration of a drug in the body after dosing....
by around 50%.