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| __NOTOC__
| | #REDIRECT [[Ticagrelor#Adverse Reactions]] |
| {{Ticagrelor}}
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| {{CMG}}; {{AE}} {{JH}}
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| ==Adverse Reactions==
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| ===Dyspnea===
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| Because [[clinical trials]] are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
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| BRILINTA has been evaluated for safety in more than 10000 patients, including more than 3000 patients treated for more than 1 year.
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| ===Bleeding===
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| PLATO used the following [[bleeding]] severity categorization:
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| • ''Major bleed – fatal/life-threatening.'' Any one of the following: fatal; intracranial; intrapericardial bleed with [[cardiac tamponade]]; [[hypovolemic shock]] or severe [[hypotension]] due to [[bleeding]] and requiring pressors or surgery; clinically overt or apparent [[bleeding]] associated with a decrease in [[hemoglobin]] (Hb) of more than 5 g/dL; transfusion of 4 or more units (whole blood or packed red blood cells (PRBCs)) for [[bleeding]].
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| • ''Major bleed – other.'' Any one of the following: significantly disabling (e.g., intraocular with permanent vision loss); clinically overt or apparent [[bleeding]] associated with a decrease in Hb of 3 g/dL; transfusion of 2-3 units (whole blood or PRBCs) for [[bleeding]].
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| • ''Minor bleed.'' Requires medical intervention to stop or treat [[[[bleeding]]]] (e.g., epistaxis requiring visit to medical facility for packing).
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| • ''Minimal bleed.'' All others (e.g., bruising, [[bleeding]] gums, oozing from injection sites, etc.) not requiring intervention or treatment.
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| Figure 1 shows major [[bleeding]] events over time. Many events are early, at a time of [[coronary angiography]], [[PCI]], CABG, and other procedures, but the risk persists during later use of antiplatelet therapy.
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| Figure 1- Kaplan-Meier estimate of time to first PLATO-defined ‘Total Major’ [[bleeding]] event
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| {|
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| |[[File:Ticagrelor01.png|thumb|800px]]
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| Annualized rates of [[bleeding]] are summarized in Table 1 below. About half of the [[bleeding]] events were in the first 30 days.
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| |[[File:Ticagrelor_02.png|thumb|800px]]
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| As shown in Table 1, BRILINTA was associated with a somewhat greater risk of non- CABG [[bleeding]] than was clopidogrel. No baseline demographic factor altered the relative risk of [[bleeding]] with BRILINTA compared to clopidogrel.
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| In PLATO, 1584 patients underwent CABG surgery. The percentages of those patients who bled are shown in Table 2. Rates were very high but similar for BRILINTA and clopidogrel.
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| {|
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| |[[File:Ticagrelor_03.png|thumb|800px]]
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| Although the platelet inhibition effect of BRILINTA has a faster offset than [[clopidogrel]] in in vitro tests and BRILINTA is a reversibly binding P2Y12 inhibitor, PLATO did not show an advantage of BRILINTA compared to clopidogrel for CABG-related [[bleeding]]. When antiplatelet therapy was stopped 5 days before CABG, major [[bleeding]] occurred in 75% of BRILINTA treated patients and 79% on clopidogrel.
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| No data exist with BRILINTA regarding a hemostatic benefit of platelet transfusions.
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| Drug Discontinuation
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| In PLATO, the rate of study drug discontinuation attributed to adverse reactions was 7.4% for BRILINTA and 5.4% for clopidogrel. [[bleeding]] caused permanent discontinuation of study drug in 2.3% of BRILINTA patients and 1.0% of clopidogrel patients. Dyspnea led to study drug discontinuation in 0.9% of BRILINTA and 0.1% of clopidogrel patients.
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| ===Common Adverse Events===
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| A variety of non-hemorrhagic adverse events occurred in PLATO at rates of 3% or more. These are shown in Table 3. In the absence of a placebo control, whether these are drug related cannot be determined in most cases, except where they are more common on BRILINTA or clearly related to the drug’s pharmacologic effect ([[dyspnea]]).
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| {|
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| |[[File:Ticagrelor_04.png|thumb|800px]]
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| ===Bradycardia===
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| In clinical studies BRILINTA has been shown to increase the occurrence of Holter-detected bradyarrhythmias (including ventricular pauses). PLATO excluded patients at increased risk of bradycardic events (e.g., patients who have sick sinus syndrome, 2nd or 3rd degree AV block, or bradycardic-related syncope and not protected with a pacemaker). In PLATO, syncope, pre-syncope and loss of consciousness were reported by 1.7% and 1.5% of BRILINTA and clopidogrel patients, respectively.
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| In a Holter substudy of about 3000 patients in PLATO, more patients had ventricular pauses with BRILINTA (6.0%) than with clopidogrel (3.5%) in the acute phase; rates were 2.2% and 1.6% respectively after 1 month.
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| ===Gynecomastia===
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| In PLATO, gynecomastia was reported by 0.23% of men on BRILINTA and 0.05% on [[clopidogrel]].
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| Other sex-hormonal adverse reactions, including sex organ malignancies, did not differ between the two treatment groups in PLATO.
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| Lab abnormalities
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| ===Serum Uric Acid related Effects:===
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| Serum uric acid levels increased approximately 0.6 mg/dL from baseline on BRILINTA and approximately 0.2 mg/dL on clopidogrel in PLATO. The difference disappeared within 30 days of discontinuing treatment. Reports of gout did not differ between treatment groups in PLATO (0.6% in each group).
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| ===Serum Creatinine related Effects:===
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| In PLATO, a >50% increase in serum creatinine levels was observed in 7.4% of patients receiving BRILINTA compared to 5.9% of patients receiving clopidogrel. The increases typically did not progress with ongoing treatment and often decreased with continued therapy. Evidence of reversibility upon discontinuation was observed even in those with the greatest on treatment increases. Treatment groups in PLATO did not differ for renal-related serious adverse events such as [[acute renal failure]], [[chronic renal failure]], toxic nephropathy, or oliguria.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BRILINTA (TICAGRELOR) TABLET [ASTRAZENECA LP] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f7b3f443-e83d-4bf2-0e96-023448fed9a8 | publisher = | date = | accessdate = 26 February 2014 }}</ref>
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| <ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BRILINTA (TICAGRELOR) TABLET [ASTRAZENECA LP] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f7b3f443-e83d-4bf2-0e96-023448fed9a8 | publisher = | date = | accessdate = 26 February 2014 }}</ref>
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| ==References==
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| <ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BRILINTA (TICAGRELOR) TABLET [ASTRAZENECA LP] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f7b3f443-e83d-4bf2-0e96-023448fed9a8 | publisher = | date = | accessdate = 26 February 2014 }}</ref>
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| {{Reflist|2}}
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| {{Antithrombotics}}
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| [[Category:ADP receptor inhibitors]]
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| [[Category:Triazolopyrimidines]]
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| [[Category:Organofluorides]]
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| [[Category:Alcohols]]
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| [[Category:AstraZeneca]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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