Training Example: ZOMIG – Review the Data, Give Your Score & Compare to the Real AI Evaluation

[H1] FULL PRESCRIBING INFORMATION
[H1] 1 INDICATIONS AND USAGE
ZOMIG Nasal Spray is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.
Limitations of Use
Only use ZOMIG if a clear diagnosis of migraine has been established. If a patient has no response to ZOMIG treatment for the first migraine attack, reconsider the diagnosis of migraine before ZOMIG is administered to treat any subsequent attacks.
ZOMIG is not indicated for the prevention of migraine attacks.
Safety and effectiveness of ZOMIG have not been established for cluster headache.
Not recommended in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.2)].
[H1] 2 DOSAGE AND ADMINISTRATION
[H2] 2.1 Dosing Information
The recommended starting dose for ZOMIG nasal spray in adult and pediatric patients 12 years of age and older is 2.5 mg. As the individual response to ZOMIG nasal spray may vary, the dose should be adjusted on an individual basis. The maximum recommended single dose of ZOMIG is 5 mg.
If the migraine has not resolved by 2 hours after taking ZOMIG, or returns after a transient improvement, another dose may be administered at least 2 hours after the previous dose.
The maximum daily dose should not exceed 10 mg in any 24-hour period.
The safety of ZOMIG in the treatment of an average of more than four headaches in a 30-day period has not been established.
[H2] 2.2 Dosing in Patients with Hepatic Impairment
ZOMIG nasal spray is not recommended in patients with moderate to severe hepatic impairment because of increased zolmitriptan blood levels in these patients and elevation of blood pressure in some of these patients. The recommended dosage of ZOMIG nasal spray in patients with mild hepatic impairment is the same as for patients with normal hepatic function [see Dosage and Administration (2.1), Warnings and Precautions (5.8), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
[H2] 2.3 Dosing in Patients taking Cimetidine
If ZOMIG is co-administered with cimetidine, limit the maximum single dose of ZOMIG to 2.5 mg, not to exceed 5 mg in any 24-hour period [see Drug Interactions (7.4) and Clinical Pharmacology (12.3)].
[H1] 3 DOSAGE FORMS AND STRENGTHS
Nasal Spray 2.5 mg and 5 mg.
[H1] 4 CONTRAINDICATIONS
ZOMIG is contraindicated in patients with:
Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), other significant underlying cardiovascular disease, or coronary artery vasospasm including Prinzmetal's angina [see Warnings and Precautions (5.1)]
Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)]
History of stroke, transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at higher risk of stroke [see Warnings and Precautions (5.4)]
Peripheral vascular disease (PVD) [see Warnings and Precautions (5.5)]
Ischemic bowel disease [see Warnings and Precautions (5.5)]
Uncontrolled hypertension [see Warnings and Precautions (5.8)]
Recent use (i.e., within 24 hours) of another 5-HT1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions (7.1, 7.3)]
Concurrent administration of an MAO-A inhibitor or recent discontinuation of a MAO-A inhibitor (that is within 2 weeks) [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]
Known hypersensitivity to ZOMIG (angioedema and anaphylaxis seen) [see Adverse Reactions (6.2)]
[H1] 5 WARNINGS AND PRECAUTIONS
[H2] 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina
ZOMIG is contraindicated in patients with ischemic or vasospastic coronary artery disease (CAD). There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of ZOMIG. Some of these reactions occurred in patients without known CAD. 5-HT1 agonists including ZOMIG may cause coronary artery vasospasm (Prinzmetal's Angina), even in patients without a history of CAD.
Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ZOMIG. Do not administer ZOMIG if there is evidence of CAD or coronary artery vasospasm [see Contraindications (4)]. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administrating the first ZOMIG dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following ZOMIG administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of ZOMIG.
[H2] 5.2 Arrhythmias
Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue ZOMIG if these disturbances occur. Patients with Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders should not receive ZOMIG [see Contraindications (4)].
[H2] 5.3 Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure
As with other 5-HT1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with ZOMIG and is usually non-cardiac in origin. However, if a cardiac origin is suspected, patients should be evaluated. Patients shown to have CAD and those with Prinzmetal's variant angina should not receive 5-HT1 agonists [see Contraindications (4)].
[H2] 5.4 Cerebrovascular Events
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. Discontinue ZOMIG if a cerebrovascular event occurs.
As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, other potentially serious neurological conditions should be excluded. ZOMIG should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications (4)].
[H2] 5.5 Other Vasospasm Reactions
5-HT1 agonists, including ZOMIG, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of vasospasm reaction following the use of any 5-HT1 agonist, the suspected vasospasm reaction should be ruled out before receiving additional ZOMIG doses [see Contraindications (4)].
Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.
[H2] 5.6 Medication Overuse Headache
Overuse of acute migraine drugs (e.g. ergotamine, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches, or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
[H2] 5.7 Serotonin Syndrome
Serotonin syndrome may occur with triptans, including ZOMIG, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually rapidly occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. ZOMIG treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions (7.5) and Patient Counseling Information (17)].
[H2] 5.8 Increase in Blood Pressure
Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT1 agonists including patients without a history of hypertension. Very rarely these increases in blood pressure have been associated with significant clinical events. In healthy subjects treated with 5 mg of ZOMIG oral tablet, an increase of 1 and 5 mm Hg in the systolic and diastolic blood pressure, respectively, was seen. In a study of patients with moderate to severe liver impairment, 7 of 27 patients experienced 20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a dose of 10 mg of ZOMIG oral tablet. As with all triptans, blood pressure should be monitored in ZOMIG-treated patients. ZOMIG is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].
[H1] 6 ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of labeling:
Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina [see Warnings and Precautions (5.1)]
Arrhythmias [see Warnings and Precautions (5.2)]
Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.3)]
Cerebrovascular Events [see Warnings and Precautions (5.4)]
Other Vasospasm Reactions [see Warnings and Precautions (5.5)]
Medication Overuse Headache [see Warnings and Precautions (5.6)]
Serotonin Syndrome [see Warnings and Precautions (5.7)]
Increase in Blood Pressure [see Warnings and Precautions (5.8)]
[H2] 6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Adults
Among 460 patients treating 1180 single attacks with ZOMIG nasal spray in a blinded placebo controlled trial (Study 1), there was a low withdrawal rate related to adverse reactions: 5 mg (1.3%), 2.5 mg (0%), and placebo (0.4%). None of the withdrawals were due to a serious event. One patient was withdrawn due to abnormal ECG changes from baseline that were incidentally found 23 days after the last dose of ZOMIG nasal spray.
The most common adverse reactions (≥ 5% and > placebo) in any dosage strength in clinical trials for ZOMIG nasal spray were: unusual taste, paresthesia, hyperesthesia, and dizziness. The incidence of adverse reactions was generally dose-related.
Table 1 lists the adverse reactions from the controlled clinical trial (Study 1) that occurred in ≥ 2% of patients in either the 2.5 or 5 mg ZOMIG nasal spray dose groups and with an incidence greater than placebo.
Table 1: Adverse reactions In a Placebo-Controlled Study In Adult Patients with Migraine (Study 1)
Body System
Adverse Reaction   Placebo
(N=228)  ZOMIG
2.5 mg
(N=224)  ZOMIG
5 mg
(N=236)
Atypical Sensations

Hyperesthesia 0%  1%  5%
Paraesthesia  6%  5%  10%
Warm Sensation  2%  4%  0%
Ear/Nose/Throat
Disorder/Discomfort of nasal cavity  2%  1%  3%
Pain and Pressure Sensations
Pain Location Specified  1%  2% 4%
Throat Pain   1%  4% 4%
Throat Tightness   1%  <1% 2%
Digestive
Dry Mouth  <1% 3% 2%
Nausea  1% 1% 4%
Neurological
Dizziness  4% 6% 3%
Somnolence  2% 1% 4%
Other
Unusual Taste 3% 17% 21%
Asthenia  1% 3% 3%
In Study 1, adverse reactions occurring in ≥ 1% and < 2% of patients in all attacks in either ZOMIG nasal spray dose group and with incidence greater than that of placebo were: abdominal pain, chills, throat pressure, facial edema, chest pressure, palpitation, dysphagia, arthralgia, myalgia, and depersonalization.
The incidence of adverse reactions in controlled clinical trials was not affected by gender, weight, or age of the patients (18-39 vs. 40-65 years of age), or presence of aura. There were insufficient data to assess the impact of race on the incidence of adverse reactions.
Local Adverse Reactions:
Among 460 patients using ZOMIG 2.5 mg or 5 mg in the controlled clinical trial, approximately 3% noted local irritation or soreness at the site of administration. Adverse reactions of any kind, perceived in the nasopharynx (which may include systemic effects of triptans) were severe in about 1% of patients and approximately 57% resolved in 1 hour. Nasopharyngeal examinations, in a subset of patients participating in two long term trials of up to one-year duration, failed to demonstrate any clinically significant changes with repeated use of ZOMIG nasal spray.
All nasopharyngeal adverse reactions with an incidence of ≥ 2% of patients in any ZOMIG nasal spray dose groups are included in Table 1.
Other Adverse Reactions:
In the paragraphs that follow, the frequencies of less commonly reported adverse clinical reactions are presented. Because the reports include reactions observed in open and uncontrolled studies, the role of ZOMIG in their causation cannot be reliably determined. Furthermore, variability associated with adverse reaction reporting, the terminology used to describe adverse reactions, etc., limit the value of the quantitative frequency estimates provided. Reaction frequencies are calculated as the number of patients who used ZOMIG nasal spray and reported a reaction divided by the total number of patients exposed to ZOMIG nasal spray (n=3059). All reported reactions are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients and rare adverse reactions are those occurring in fewer than 1/1,000 patients.
General: Infrequent: allergic reactions.
Cardiovascular: Infrequent: arrhythmias, hype