Agrylin

Name: Agrylin

Indications

AGRYLIN Capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative neoplasms, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events [see Clinical Studies, DOSAGE AND ADMINISTRATION].

Overdose

At higher than recommended doses, this medicine has been shown to cause hypotension. There have been postmarketing case reports of intentional overdose with anagrelide hydrochloride. Reported symptoms include sinus tachycardia and vomiting. Symptoms resolved with supportive management. Platelet reduction from anagrelide therapy is dose-related; therefore, thrombocytopenia, which can potentially cause bleeding, is expected from overdosage.

In case of overdosage, close clinical supervision of the patient is required; this especially includes monitoring of the platelet count for thrombocytopenia. Dosage should be stopped, as appropriate, until the platelet count returns to within the normal range.

Uses of Agrylin

Agrylin is a prescription medication used to treat a condition where the blood makes too many platelets. Too many platelets in the blood increases the risk for serious events such as a stroke, heart attack, or bleeding.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

 

Agrylin 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:

  • tazanavir (Reyataz)
  • cilostazol (Pletal)
  • cimetidine (Tagamet)
  • clozapine (Clozaril)
  • cyclobenzaprine (Flexeril)
  • fluoroquinolone antibiotics including ciprofloxacin (Cipro), gatifloxacin (Tequin), levofloxacin (Levaquin), norfloxacin (Noroxin), ofloxacin (Floxin)
  • fluvoxamine (Luvox)
  • imipramine (Tofranil)
  • inamrinone
  • mexiletine (Mexitil)
  • milrinone (Primacor)
  • naproxen (Aleve, Naprosyn, in Prevacid NapraPAC)
  • riluzole (Rilutek)
  • sucralfate (Carafate)
  • tacrine (Cognex)
  • theophylline (Elixophyllin, Theo-24, Theolair, others)
  • ticlopidine (Ticlid)

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

Agrylin Precautions

Serious side effects can occur with use of Agrylin. If you experience any of the following symptoms, call your doctor immediately:

  • rash
  • hives
  • unusual bleeding or bruising
  • blood in urine or stool
  • black or tarry stools
  • chest pain
  • fluttering sensation in the chest
  • fast, forceful, or irregular heartbeats
  • swelling of the arms, hands, feet, ankles or lower legs
  • difficulty breathing
  • cough
  • slow or difficult speech
  • fainting
  • weakness or numbness of an arm or leg
  • pain, burning, or tingling in the hands or feet
  • seizure
  • changes in vision

Do not take this medication if you:

  • are allergic to Agrylin or to any of its ingredients
  • have severe liver impairment

Do not drive or operate heavy machinery until you know how this medication affects you.

Cautions for Agrylin

Contraindications

Severe hepatic impairment.1

Warnings/Precautions

Warnings

Cardiovascular Effects

Adverse cardiovascular effects (e.g., vasodilation, tachycardia, palpitations, edema, CHF) reported with usual dosages of anagrelide, including rare cases of sudden death.1 5 16 17 18 26 Assess risk versus benefits of therapy.1 16 17 Use with caution, if at all, in patients with known or suspected cardiovascular disease.1 5 13 15 16 17 18 22 23 24 Evaluate cardiac status prior to and during therapy.1 5 13 16 17 Consider reduced dosages.5 Some clinicians recommend immediate discontinuance of therapy if any evidence of cardiac dysfunction occurs.5 26

Temporary decreases in BP reported, usually during treatment initiation; BP appears to normalize during maintenance therapy.5 9 17 23 24

General Precautions

Laboratory Monitoring

Monitor CBCs, liver function tests, and renal function tests while platelet counts are being decreased, usually during first 2 weeks of therapy.1

To assess response to therapy and prevent thrombocytopenia, monitor platelet counts every 2 days for first week of therapy, then at least weekly thereafter until maintenance dosage achieved.1 23

Rebound Thrombocythemia

A rapid (e.g., within 4 days) increase in platelet count generally is observed when anagrelide is discontinued or interrupted.1 5 16 17 18 23 Continue treatment indefinitely (if adequate response achieved) to prevent rebound thrombocythemia.17 23

Anemia

Decreases in hemoglobin and hematocrit (anemia) reported, usually with long-term use.1 5 9 10 12 13 16 17 18 24 27

Bleeding Tendency

Concomitant use with aspirin may increase bleeding tendency.3 5 6 9 (See Specific Drugs and Foods under Interactions.) Use caution with such combined therapy.3 5 6 Some clinicians suggest that aspirin not be used concomitantly with anagrelide in patients with history of bleeding.3

Renal Effects

Renal impairment reported in a few patients following treatment with anagrelide; most patients had preexisting renal impairment.1 17 23 Monitor renal function while platelet counts are being decreased.1

Fetal/Neonatal Morbidity

Safety of use during pregnancy not established; embryotoxicity and fetotoxicity demonstrated in animals.1 Generally not recommended in pregnant women unless potential benefits outweigh possible risks to fetus.1 5 11 16 22 Women of childbearing potential should avoid pregnancy and use contraception during therapy.1 5

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether anagrelide is distributed into human milk.1 Discontinue nursing or drug because of potential risk in nursing infants.1 5

Pediatric Use

Evaluated in a limited number of children and adolescents 7–14 years of age with thrombocythemia secondary to myeloproliferative disorders;1 28 29 preliminary data suggest no overall differences in dosage or adverse effects relative to adults.1

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults.1 Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function.1 5 16 22

Hepatic Impairment

Extensively metabolized in liver; possible increased systemic exposure to anagrelide in patients with hepatic impairment.1 9 (See Elimination: Special Populations, under Pharmacokinetics.)

Weigh risks of therapy against potential benefits in patients with mild to moderate hepatic impairment.1 Reduce dosage and carefully monitor for adverse cardiovascular effects or other manifestations of toxicity.1 17 22 23 (See Hepatic Impairment under Dosage and Administration and see Cardiovascular Effects under Cautions.)

Contraindicated in patients with severe hepatic impairment.1

Renal Impairment

Closely monitor patients with known or suspected renal impairment for cardiovascular effects or other manifestations of toxicity.1 17 23

Common Adverse Effects

Headache,1 3 5 7 9 10 16 17 18 23 24 palpitations,1 3 5 7 9 10 16 17 18 23 24 diarrhea,1 3 5 7 9 10 17 18 23 24 asthenia,1 9 23 edema,1 5 9 10 16 17 18 23 24 nausea,1 7 9 18 23 24 abdominal pain,1 9 17 18 23 24 dizziness,1 9 16 18 23 24 pain,1 9 dyspnea,1 9 flatulence,1 9 18 vomiting,1 9 23 fever,1 9 peripheral edema,1 9 rash,1 9 chest pain,1 23 anorexia,1 9 tachycardia,1 7 9 16 18 23 24 pharyngitis,1 9 malaise,1 9 23 cough,1 9 paresthesia,1 9 back pain,1 pruritus,1 9 dyspepsia.1 9

Uses For Agrylin

Anagrelide is used to decrease the risk of blood clots in patients who have thrombocythemia (too many platelets in the blood). It works to decrease production of platelets in the body.

This medicine is available only with your doctor's prescription.

Before Using Agrylin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of anagrelide in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of anagrelide in the elderly.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Amifampridine
  • Amisulpride
  • Bepridil
  • Cisapride
  • Defibrotide
  • Dronedarone
  • Mesoridazine
  • Pimozide
  • Piperaquine
  • Saquinavir
  • Sparfloxacin
  • Terfenadine
  • Thioridazine
  • Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Abciximab
  • Abiraterone
  • Aceclofenac
  • Acemetacin
  • Alfuzosin
  • Alipogene Tiparvovec
  • Amiodarone
  • Amitriptyline
  • Amtolmetin Guacil
  • Apixaban
  • Apomorphine
  • Ardeparin
  • Argatroban
  • Aripiprazole
  • Aripiprazole Lauroxil
  • Arsenic Trioxide
  • Asenapine
  • Aspirin
  • Astemizole
  • Atazanavir
  • Azithromycin
  • Balofloxacin
  • Bedaquiline
  • Bemiparin
  • Besifloxacin
  • Betrixaban
  • Bivalirudin
  • Bromfenac
  • Bufexamac
  • Buserelin
  • Celecoxib
  • Certoparin
  • Chloroquine
  • Chlorpromazine
  • Choline Salicylate
  • Cilostazol
  • Ciprofloxacin
  • Citalopram
  • Clarithromycin
  • Clomipramine
  • Clonixin
  • Clopidogrel
  • Clozapine
  • Crizotinib
  • Cyclobenzaprine
  • Dabigatran Etexilate
  • Dabrafenib
  • Dalteparin
  • Danaparoid
  • Dasatinib
  • Degarelix
  • Delamanid
  • Desipramine
  • Desirudin
  • Deslorelin
  • Desvenlafaxine
  • Deutetrabenazine
  • Dexibuprofen
  • Dexketoprofen
  • Diclofenac
  • Diflunisal
  • Dipyridamole
  • Dipyrone
  • Disopyramide
  • Dofetilide
  • Dolasetron
  • Domperidone
  • Donepezil
  • Doxepin
  • Droperidol
  • Droxicam
  • Duloxetine
  • Ebastine
  • Edoxaban
  • Efavirenz
  • Enoxacin
  • Enoxaparin
  • Enoximone
  • Eptifibatide
  • Eribulin
  • Erythromycin
  • Escitalopram
  • Ethinyl Estradiol
  • Etodolac
  • Etofenamate
  • Etoricoxib
  • Famotidine
  • Felbamate
  • Felbinac
  • Fenoprofen
  • Fepradinol
  • Feprazone
  • Fingolimod
  • Flecainide
  • Floctafenine
  • Fluconazole
  • Flufenamic Acid
  • Flumequine
  • Fluoxetine
  • Flurbiprofen
  • Fluvoxamine
  • Fondaparinux
  • Formoterol
  • Foscarnet
  • Fosphenytoin
  • Galantamine
  • Gatifloxacin
  • Gemifloxacin
  • Gonadorelin
  • Goserelin
  • Granisetron
  • Halofantrine
  • Haloperidol
  • Heparin
  • Histrelin
  • Hydroquinidine
  • Hydroxychloroquine
  • Hydroxyzine
  • Ibuprofen
  • Ibutilide
  • Iloperidone
  • Imipramine
  • Inamrinone
  • Indomethacin
  • Itraconazole
  • Ivabradine
  • Ketoconazole
  • Ketoprofen
  • Ketorolac
  • Lapatinib
  • Lepirudin
  • Leuprolide
  • Levofloxacin
  • Levomilnacipran
  • Lomefloxacin
  • Lornoxicam
  • Loxoprofen
  • Lumefantrine
  • Lumiracoxib
  • Meclofenamate
  • Mefenamic Acid
  • Mefloquine
  • Meloxicam
  • Methadone
  • Methoxsalen
  • Metronidazole
  • Mexiletine
  • Mibefradil
  • Mifepristone
  • Milnacipran
  • Milrinone
  • Mizolastine
  • Morniflumate
  • Moxifloxacin
  • Nabumetone
  • Nadifloxacin
  • Nadroparin
  • Nafarelin
  • Naproxen
  • Nelfinavir
  • Nepafenac
  • Niflumic Acid
  • Nilotinib
  • Nimesulide
  • Nimesulide Beta Cyclodextrin
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Olanzapine
  • Ondansetron
  • Oxaprozin
  • Oxyphenbutazone
  • Paliperidone
  • Panobinostat
  • Parecoxib
  • Parnaparin
  • Paroxetine
  • Pasireotide
  • Pazopanib
  • Pazufloxacin
  • Pefloxacin
  • Peginterferon Alfa-2b
  • Pentamidine
  • Perphenazine
  • Phenindione
  • Phenprocoumon
  • Phenylbutazone
  • Phenylpropanolamine
  • Piketoprofen
  • Pimavanserin
  • Pipamperone
  • Piracetam
  • Piroxicam
  • Pitolisant
  • Pixantrone
  • Posaconazole
  • Prasugrel
  • Probucol
  • Procainamide
  • Prochlorperazine
  • Proglumetacin
  • Promethazine
  • Propafenone
  • Propyphenazone
  • Proquazone
  • Protein C
  • Protriptyline
  • Prulifloxacin
  • Quetiapine
  • Quinidine
  • Quinine
  • Ranolazine
  • Reviparin
  • Ribociclib
  • Rilpivirine
  • Risperidone
  • Ritonavir
  • Rivaroxaban
  • Rofecoxib
  • Rufloxacin
  • Salicylic Acid
  • Salsalate
  • Sertindole
  • Sertraline
  • Sevoflurane
  • Sodium Phosphate
  • Sodium Phosphate, Dibasic
  • Sodium Phosphate, Monobasic
  • Sodium Salicylate
  • Solifenacin
  • Sorafenib
  • Sotalol
  • Sulfinpyrazone
  • Sulindac
  • Sulpiride
  • Sunitinib
  • Tacrolimus
  • Tamoxifen
  • Telaprevir
  • Telavancin
  • Telithromycin
  • Tenoxicam
  • Tetrabenazine
  • Thiabendazole
  • Tiaprofenic Acid
  • Ticagrelor
  • Ticlopidine
  • Tinzaparin
  • Tirofiban
  • Tizanidine
  • Tolfenamic Acid
  • Tolmetin
  • Tolterodine
  • Toremifene
  • Trazodone
  • Treprostinil
  • Trimipramine
  • Triptorelin
  • Valdecoxib
  • Vandetanib
  • Vardenafil
  • Vemurafenib
  • Venlafaxine
  • Vilanterol
  • Vilazodone
  • Vinflunine
  • Voriconazole
  • Vorinostat
  • Vortioxetine
  • Warfarin
  • Zileuton
  • Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bleeding problems or
  • Congestive heart failure, history of or
  • Heart disease, history of or
  • Heart rhythm problems, history of or
  • Hypotension (low blood pressure) or
  • Kidney disease or
  • Lung disease (eg, interstitial lung disease), history of—Use with caution. May make these conditions worse.
  • Liver disease, mild or moderate—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
  • Heart rhythm problem (eg, congenital long QT syndrome, QT prolongation) or
  • Hypokalemia (low potassium in the blood) or
  • Liver disease, severe—Should not be used in patients with this condition.

Agrylin Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • body aches or pain
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chest pain
  • congestion
  • cough
  • difficult or labored breathing
  • dryness or soreness of the throat
  • fast, irregular, pounding, or racing heartbeat or pulse
  • fever
  • hoarseness
  • rapid weight gain
  • runny nose
  • tender, swollen glands in the neck
  • tightness in the chest
  • trouble with swallowing
  • voice changes
Less common
  • Anxiety
  • blurred vision
  • burning while urinating
  • chills
  • cold sweats
  • confusion
  • decreased urine output
  • dehydration
  • difficult or painful urination
  • dilated neck veins
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • extreme fatigue
  • general feeling of discomfort or illness
  • headache
  • irregular breathing
  • joint pain
  • large, flat, blue, or purplish patches in the skin
  • loss of appetite
  • muscle aches and pains
  • nausea or vomiting
  • noisy breathing
  • pale skin
  • redness of the face, neck, arms, and occasionally, upper chest
  • severe pain or pressure in the chest or the jaw, neck, back, or arms
  • sudden severe headache or weakness
  • swollen, painful, or tender lymph glands in the neck, armpit, or groin
  • trouble sleeping
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • vomiting of blood or material that looks like coffee grounds
  • weight gain
Incidence not known
  • Abdominal or stomach pain or tenderness
  • clay colored stools
  • dark urine
  • decreased appetite
  • dry cough
  • general feeling of tiredness or weakness
  • rapid breathing
  • skin rash or itching
  • yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Acid or sour stomach
  • back pain
  • belching
  • diarrhea
  • excess air or gas in the stomach or intestines
  • full feeling
  • general feeling of discomfort or illness
  • heartburn
  • hives or welts
  • indigestion
  • lack or loss of strength
  • pain
  • passing gas
  • stomach discomfort, upset, or pain
Less common
  • Burning feeling in the chest or stomach
  • change in vision
  • confusion
  • constipation
  • continuing ringing or buzzing or other unexplained noise in the ears
  • depression
  • difficulty with moving
  • double vision
  • hair loss or thinning of the hair
  • hearing loss
  • impaired vision
  • increased sensitivity of the skin to sunlight
  • leg cramps
  • loss of memory
  • muscle pain or stiffness
  • problems with memory
  • redness or other discoloration of the skin
  • seeing double
  • severe sunburn
  • sleepiness or unusual drowsiness
  • stuffy nose
  • swelling or inflammation of the mouth
  • swollen joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses of Agrylin

  • It is used to lower platelet count.

Indications and Usage for Agrylin

Agrylin Capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative neoplasms, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events [see Clinical Studies (14), Dosage and Administration (2)].

Agrylin Description

Agrylin (anagrelide hydrochloride) is a platelet-reducing agent. Its chemical name is 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one monohydrochloride monohydrate. The molecular formula is C10H7Cl2N3O∙HCl∙H2O which corresponds to a molecular weight of 310.55. The structural formula is:

Anagrelide hydrochloride is an off-white powder. It is very slightly soluble in water and sparingly soluble in dimethyl sulfoxide and dimethylformamide.

Agrylin is supplied as capsules for oral administration, containing 0.5 mg of anagrelide base (as anagrelide hydrochloride). The capsules also contain anhydrous lactose NF, crospovidone NF, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, and povidone NF as inactive ingredients. The capsule shell contains gelatin, titanium dioxide and black iron oxide.

Adverse Effects

>10%

Headache (44%)

Palpitations (26%)

Diarrhea (26%)

Asthenia (23%)

Edema (21%)

Nausea (17%)

Abdominal pain (16%)

Dizziness (15%)

General pain (15%)

Dyspnea (12%)

1-10%

Flatulence (10%)

Vomiting (10%)

Fever (9%)

Edema (9%)

Rash (8%)

Chest pain (8%)

Anorexia (8%)

Tachycardia (8%)

Pharyngitis (7%)

Malaise (6%)

Cough (6%)

Paresthesia (6%)

Back pain (6%)

Pruritus (6%)

Confusion (1-5%)

Depression

Migraine

Myalgia

Nervousness

Photosensitivity

Arthralgia

Vision abnormalities

Angina

Arrhythmia

Cardiovascular disease

Heart failure

Hemorrhage

Hypertension

Postural hypotension

Syncope

Thrombosis

Vasodilation

Bronchitis

Rhinitis

Sinusitis

Constipation

Dyspepsia

Gastritis

Anemia

Elevated liver enzymes

Flu symptoms

Leg cramps

Dehydration

Postmarketing Reports

Interstitial lung diseases, including allergic alveolitis, eosinophilic pneumonia and interstitial pneumonitis

Hepatotoxicity

Tubulointerstitial nephritis

Supraventricular tachycardia (SVT)

Hypoesthesia

Torsades de pointes

Pregnancy & Lactation

Pregnancy Category: C

Lactation: excretion in milk unknown/not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What is anagrelide (agrylin)?

Anagrelide lowers the number of blood clotting cells (platelets) in the body, which helps prevent blood clots from forming.

Anagrelide is used to treat a condition called thrombocythemia (also called thrombocytosis). Thrombocythemia is a blood cell disorder in which too many platelet cells are produced, causing bleeding or blood-clotting problems.

Anagrelide may also be used for purposes not listed in this medication guide.

What is the most important information i should know about anagrelide (agrylin)?

You should not use anagrelide if you are allergic to it, or if you have moderate to severe liver disease.

Before you take anagrelide, tell your doctor if you have heart disease, kidney disease, or liver disease.

To be sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your kidney and liver function may also need to be tested. Visit your doctor regularly. Tell any doctor or dentist who treats you that you are taking anagrelide, especially if you need to have any type of surgery.

Do not stop taking this medication without first talking to your doctor. Stopping suddenly can make your condition worse very quickly.

Call your doctor at once if you have a serious side effect such as dry cough, trouble breathing, swelling, fast or pounding heartbeats, chest pain, sudden numbness or weakness, confusion, problems with speech or balance, severe stomach pain, seizure, fainting, blood in your urine or stools, easy bruising or bleeding, or unusual weakness.

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