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Home > Medications (Drugs) > Anagrelide > Interactions with Anagrelide

Interactions with Anagrelide

If you are currently being treated with any of the following medications, you should not use Anagrelide without reading these interactions.

Rasagiline

ADJUST DOSE: Coadministration with drugs that are inhibitors of CYP450 1A2 may increase the plasma concentrations of rasagiline, which is a substrate of the isoenzyme. In 12 healthy volunteers, coadministration with ciprofloxacin (500 mg twice a day) increased the systemic exposure (AUC) of rasagiline (2 mg once a day) by 83%, with no change in elimination half-life.

MANAGEMENT: Patients treated concomitantly with potent inhibitors of CYP450 1A2 such as ciprofloxacin or fluvoxamine should use rasagiline 0.5 mg/day. Patients receiving other CYP450 1A2 inhibitors should initiate therapy at the lower dosage, then increase gradually as necessary.

Alosetron (oral)

GENERALLY AVOID: Coadministration with inhibitors of CYP450 1A2 may increase the plasma concentrations of alosetron, which has been shown in vivo to be predominantly metabolized by the isoenzyme. In 40 healthy female subjects, pretreatment with the potent CYP450 1A2 inhibitor fluvoxamine (in escalating doses from 50 to 200 mg/day for 16 days) increased the area under the plasma concentration-time curve (AUC) and half-life of alosetron (1 mg single oral dose) by approximately 6-fold and 3-fold, respectively. Fluvoxamine is known to also inhibit CYP450 2C9 and 3A4, both of which have been shown in vitro to be involved in the metabolism of alosetron. However, it is uncertain to what extent inhibition of these isoenzymes actually contribute to the interaction. Concomitant administration of alosetron with moderate CYP450 1A2 inhibitors such as quinolone antibiotics and cimetidine has not been evaluated.

MANAGEMENT: Because alosetron is associated with potentially serious and life-threatening, dose-related gastrointestinal adverse effects, concomitant use with CYP450 1A2 inhibitors should generally be avoided if possible (use with fluvoxamine is specifically contraindicated). If concurrent administration is necessary, it may be appropriate to initially prescribe a lower dosage of alosetron (e.g., 1 mg once a day). However, the product labeling does not offer recommendations for a dosage adjustment. Patients should be advised to immediately discontinue alosetron and notify their physician if they experience constipation or signs and symptoms of ischemic colitis such as rectal bleeding, bloody diarrhea, and new or worsening abdominal pain. Alosetron should not be resumed if ischemic colitis is diagnosed. Ischemic colitis and other serious complications such as obstruction, perforation, impaction, and toxic megacolon have resulted in hospitalization, blood transfusion, surgery, and death.

Ardeparin, Tinzaparin, Fondaparinux (injectable)

GENERALLY AVOID: Drugs that can affect hemostasis such as dextran, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or other anticoagulants may potentiate the risk of bleeding complications associated with the use of a low molecular weight heparin (LMWH), heparinoid, or fondaparinux. In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during LMWH, heparinoid, or fondaparinux therapy may also be increased by the concomitant use of other drugs that affect coagulation. The development of epidural and spinal hematoma can lead to long-term or permanent paralysis.

MANAGEMENT: In general, any agent that can enhance the risk of hemorrhage including other anticoagulants should be discontinued prior to initiation of LMWH, heparinoid, or fondaparinux therapy. If coadministration is necessary, it should be undertaken with caution and only after thorough assessment of risks and benefits. Close clinical and laboratory observation for bleeding complications is recommended. Patients undergoing neuraxial intervention and treated with these agents should also be monitored frequently for signs and symptoms of neurologic impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), and bowel or bladder dysfunction.

Cilostazol

MONITOR: Anagrelide is an inhibitor of cyclic AMP phosphodiesterase (PDE) III and may potentiate the pharmacologic effects of drugs with similar properties such as inotropes milrinone, enoximone, inamrinone, olprinone, and cilostazol. Anagrelide alone has been associated with cardiovascular side effects such as vasodilation, palpitations, tachycardia, congestive heart failure, myocardial infarction, cardiomyopathy, cardiomegaly, complete heart block, and atrial fibrillation.

MANAGEMENT: Caution is advised if anagrelide is coadministered with other inotropes or PDE III inhibitors. The risk of potentially additive cardiovascular adverse effects should be considered.

Dasatinib

MONITOR CLOSELY: Coadministration of dasatinib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Treatment with dasatinib is associated with severe thrombocytopenia. In addition, dasatinib has been shown to induce platelet dysfunction in vitro. Severe central nervous system hemorrhages, including fatalities, occurred in 1% of patients receiving dasatinib in clinical trials. Severe gastrointestinal hemorrhage occurred in 7% of patients and generally required treatment interruptions and transfusions. Other cases of severe hemorrhage occurred in 4% of patients. Most bleeding events were associated with severe thrombocytopenia.

MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with dasatinib. Close clinical and laboratory observation for bleeding complications is recommended during therapy. A complete blood count (CBC) with differential and platelet count should be obtained prior to and at least weekly for the first 2 months, then monthly thereafter or as clinically indicated. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Ibritumomab

MONITOR CLOSELY: Coadministration of ibritumomab and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Ibritumomab commonly causes severe and prolonged thrombocytopenia, and the risk is increased further in patients with mild thrombocytopenia at the initiation of therapy. Hemorrhage, including fatal cerebral hemorrhage, has occurred in a minority of patients in clinical studies. The median time to thrombocyte nadir was 7 to 9 weeks, and the median duration of thrombocytopenia was 22 to 35 days. However, in less than 5% of the cases, patients experienced severe cytopenia that extended beyond 12 weeks following administration of the ibritumomab therapeutic regimen. Platelet transfusions were given to 22% of patients in clinical trials.

MANAGEMENT: Caution is advised if ibritumomab is used in combination with drugs that interfere with platelet function or coagulation. Close clinical and laboratory observation for bleeding complications is recommended during and after ibritumomab therapy.

Tirofiban, Eptifibatide

MONITOR CLOSELY: The combination of glycoprotein IIb/IIIa inhibitors and anagrelide can theoretically significantly increase the risk of bleeding. GP IIb/IIIa inhibitors inhibit platelet aggregation by blocking the fibrinogen, von Willebrand factor, and other adhesive ligands to platelets. The mechanism whereby anagrelide decreases platelet concentrations is not known. The combination of these drugs, therefore, could decrease platelet number and function.

MANAGEMENT: Extraordinary precautions are recommended if these drugs must be used together, including monitoring platelet counts and hemoglobin concentrations. In addition, invasive procedures, such as urinary catheterization, nasogastric or nasotracheal intubation, and even venous punctures should be avoided or minimized. Non-compressible venous access sites, such as jugular or subclavian sites, should be avoided.

Tipranavir

MONITOR CLOSELY: Theoretically, tipranavir may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. Tipranavir has been shown to inhibit human platelet aggregation in vitro at levels consistent with exposures observed in patients receiving tipranavir/ritonavir. Cases of intracranial hemorrhage, some fatal, have been reported during postmarketing use. However, many of these patients had other medical conditions or were receiving concomitant medications that may have caused or contributed to these events. No pattern of abnormal coagulation parameters has been observed in patients in general, or preceding the development of intracranial hemorrhage.

MANAGEMENT: Caution is advised if tipranavir/ritonavir is used in combination with other drugs that affect hemostasis. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Ropinirole (oral)

MONITOR: Coadministration with drugs that are inhibitors of CYP450 1A2 may increase the plasma concentrations of ropinirole, which is metabolized by the isoenzyme. Ciprofloxacin (500 mg twice a day), a known inhibitor of CYP450 1A2, has been reported to increase the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ropinirole (2 mg three times a day) by an average of 60% and 84%, respectively, in 12 study subjects. The possibility of prolonged and/or increased pharmacologic effects of ropinirole should be considered.

MANAGEMENT: Pharmacologic response to ropinirole should be monitored more closely whenever a CYP450 1A2 inhibitor is added to or withdrawn from therapy, and the ropinirole dosage adjusted as necessary. Patients should be advised to contact their physician if they experience excessive adverse effects of ropinirole such as agitation, hallucinations, orthostasis, sedation, confusion, or increased dyskinesia, flushing, dry mouth, sweating, and heart rate.

Sibutramine (oral), Citalopram (oral), Escitalopram

MONITOR: Serotonin reuptake inhibitors (SRIs) may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. The tricyclic antidepressant, clomipramine, is also a strong SRI and may interact similarly. Serotonin release by platelets plays an important role in hemostasis, thus SRIs may alter platelet function and induce bleeding. Published case reports have documented the occurrence of bleeding episodes in patients treated with psychotropic agents that interfere with serotonin reuptake. Additional epidemiological studies have confirmed the association between use of these agents and the occurrence of upper gastrointestinal bleeding, and concurrent use of NSAIDs or aspirin was found to potentiate the risk. Preliminary data also suggest that there may be a pharmacodynamic interaction between SSRIs and oral anticoagulants that can cause an increased bleeding diathesis. Concomitant administration of paroxetine and warfarin, specifically, has been associated with an increased frequency of bleeding without apparent changes in the disposition of either drug or changes in the prothrombin time. Bleeding has also been reported with fluoxetine and warfarin, while citalopram and sertraline have been reported to prolong the prothrombin time of patients taking warfarin by about 5% to 8%.

MANAGEMENT: Caution is advised if SRIs or clomipramine are used in combination with other drugs that affect hemostasis. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Meloxicam, Diclofenac topical, Bromfenac (ophthalmic), Nepafenac ophthalmic

MONITOR: Systemically and topically administered nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of bleeding in patients treated with anticoagulants and other drugs that affect hemostasis such as platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. The pharmacologic effects of NSAIDs that contribute to this interaction include prolongation of prothrombin time and inhibition of platelet adhesion and aggregation.

MANAGEMENT: Caution is advised if NSAIDs are used in combination with other drugs that affect hemostasis. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Interferon alfacon-1, Grepafloxacin, Rofecoxib (oral), Peginterferon alfa-2b, Peginterferon alfa-2a

MONITOR: Theoretically, coadministration with drugs that are inhibitors of CYP450 1A2 may increase the plasma concentrations of anagrelide, which is a substrate of the isoenzyme.

MANAGEMENT: Clinicians should recognize the potential for interaction with drugs that inhibit CYP450 1A2 and monitor for evidence of anagrelide toxicities during coadministration. Since platelet reduction from anagrelide therapy is dose-related, thrombocytopenia may occur due to reduced clearance of anagrelide and may be a sign of overdosage. Patients should also be monitored for cardiovascular adverse effects such as tachycardia, palpitations, hypotension, edema, and congestive heart failure.

Iloprost

MONITOR: Theoretically, iloprost may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. Iloprost inhibits platelet aggregation. In clinical trials, hemoptysis occurred in 5% of the patients receiving iloprost compared to 2% of patients receiving placebo.

MANAGEMENT: Caution is advised if iloprost is used in combination with other drugs that affect hemostasis. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Treprostinil

MONITOR: Theoretically, treprostinil may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. Treprostinil inhibits platelet aggregation. However, patients received concomitant anticoagulants and nonsteroidal anti-inflammatory agents without increased bleeding in clinical trials.

MANAGEMENT: Caution is advised if treprostinil is used in combination with other drugs that affect hemostasis. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Chamomile, Fenugreek

Some herbs such as chamomile and fenugreek have coumarin constituents. Theoretically, ingesting large quantities of these herbs may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. However, their effects on the coagulation system have not been studied, and bleeding complications have not been reported in humans. Moreover, pharmacologic effects may be highly variable due to inconsistencies in formulation and potency of commercial herbal products. In one patient, the addition of boldo and fenugreek to a stabilized regimen of warfarin resulted in an increase in INR. The INR returned to normal 1 week following discontinuation of both products but increased again when the patient resumed usage, which subsequently led to a 15% reduction in the weekly warfarin dosage. It is not certain whether the effects on INR are due to boldo or fenugreek, or a combination of both products. Patients should consult a healthcare provider before taking any herbal or alternative medicine. In patients who have used chamomile or fenugreek extensively prior to receiving anticoagulation, antiplatelet or thrombolytic therapy, the potential for an interaction should be considered. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Capsicum

Theoretically, capsicum may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. Animal and limited human data suggest that capsicum may increase fibrinolytic activity, lower plasma fibrinogen levels, increase plasma antithrombin III levels, inhibit platelet aggregation, and prolong bleeding time. However, bleeding complications and interactions with hematologic agents have not been reported. Moreover, pharmacologic effects of capsicum preparations may be highly variable due to inconsistencies in formulation and potency of commercial herbal products. Patients should consult a healthcare provider before taking any herbal or alternative medicine. In patients who have used capsicum extensively prior to receiving anticoagulation, antiplatelet, or thrombolytic therapy, the potential for an interaction should be considered. Clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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