Zolmitriptan (Page 5 of 6)

14 CLINICAL STUDIES

Zolmitriptan Tablets

The efficacy of zolmitriptan tablets in the acute treatment of migraine headaches was demonstrated in five randomized, double-blind, placebo-controlled studies (Studies 1, 2, 3, 4, and 5), of which two utilized the 1 mg dose, two utilized the 2.5 mg dose and four utilized the 5 mg dose. In Study 1, patients treated their headaches in a clinic setting. In the other studies, patients treated their headaches as outpatients. In Study 4, patients who had previously used sumatriptan were excluded, whereas in the other studies no such exclusion was applied.

Patients enrolled in these 5 studies were predominantly female (82%) and Caucasian (97%) with a mean age of 40 years (range 12 to 65). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed at 1, 2, and, in most studies, 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours post-dose. A second dose of zolmitriptan tablets or other medication was allowed 2 to 24 hours after the initial treatment for persistent and recurrent headache. The frequency and time to use of these additional treatments were also recorded. In all studies, the effect of zolmitriptan tablets was compared to placebo in the treatment of a single migraine attack.

In all five studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater among patients who received zolmitriptan tablets at all doses (except for the 1 mg dose in the smallest study) compared to those who received placebo. In Studies 1 and 3, there was a statistically significant greater percentage of patients with headache response at 2 hours in the higher dose groups (2.5 and/or 5 mg) compared to the 1 mg dose group. There were no statistically significant differences between the 2.5 mg and 5 mg dose groups (or of doses up to 20 mg) for the primary end point of headache response at 2 hours in any study. The results of these controlled clinical studies are summarized in Table 2.

Table 2 Percentage of Patients with Headache Response (Reduction in Headache Severity from Moderate or Severe Pain to Mild or No Headache) 2 Hours Following Treatment in Studies 1 through 5

n = number of patients randomized

* p<0.05 in comparison with placebo.

c p<0.05 in comparison with 1 mg.

a Study 1 was the only study in which patients treated the headache in a clinic setting.

b Study 4 was the only study where patients were excluded who had previously used sumatriptan.

NA — not applicable

Placebo Zolmitriptantablets 1 mg Zolmitriptantablets 2.5 mg Zolmitriptantablets 5 mg
Study 1a 16% (n=19) 27% (n=22) NA 60%*# (n=20)
Study 2 19% (n=88) NA NA 66%*(n=179)
Study 3 34% (n=121) 50%* (n=140) 65%*# (n=260) 67%*# (n=245)
Study 4b 44% (n=55) NA NA 59%*(n=491)
Study 5 36% (n=92) NA 62%* (n=178) NA

The estimated probability of achieving an initial headache response by 4 hours following treatment in pooled Studies 2, 3, and 5 is depicted in Figure 1.

Figure 1 Estimated Probability of Achieving Initial Headache Response (Reduction in Headache Severity from Moderate or Severe Pain to Mild or No Headache) Within 4 Hours of Treatment in Pooled Studies 2, 3, and 5*

Image
(click image for full-size original)

* In this Kaplan-Meier plot, the averages displayed are based on pooled data from 3 placebo controlled, outpatient trials. Patients not achieving headache response or taking additional treatment prior to 4 hours were censored at 4 hours.

For patients with migraine associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of zolmitriptan tablets as compared with placebo.

Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2.

Figure 2 The Estimated Probability Of Patients Taking A Second Dose Or Other Medication For Migraines Over The 24 Hours Following The Initial Dose Of Study Treatment in Pooled Studies 2, 3, and 5*

Image
(click image for full-size original)

*In this Kaplan-Meier plot, patients not using additional treatments were censored at 24 hours. The plot includes both patients who had headache response at 2 hours and those who had no response to the initial dose. The studies did not allow taking additional doses of study medication within 2 hours post-dose.

The efficacy of zolmitriptan tablets was unaffected by presence of aura; duration of headache prior to treatment; relationship to menses; gender, age, or weight of the patient; pre-treatment nausea or concomitant use of common migraine prophylactic drugs.

16 HOW SUPPLIED/STORAGE AND HANDLING

2.5 mg Tablets — Yellow, film-coated, round, biconvex tablets debossed with ‘I ‘ on the left side and ‘G ‘ on the right side of functional score on one side and ‘458 ‘ on the other:

cartons of 6 unit-dose tablets — NDC 69097-863-17

5 mg Tablets — Pink, film-coated, round, biconvex tablets debossed with ‘IG ‘ on one side and ‘459 ‘ on the other:

cartons of 3 unit-dose tablets — NDC 69097-864-84

Store zolmitriptan tablets at controlled room temperature, 20°C to 25°C (68 °F to 77°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospastic Reactions, and Cerebrovascular Events

Inform patients that zolmitriptan tablets may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular reactions can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and instruct them to ask for medical advice when observing any indicative sign or symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5)].

Medication Overuse Headache

Inform patients that use of drugs to treat acute migraines for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6) ].

Serotonin Syndrome

Inform patients about the risk of serotonin syndrome with the use of zolmitriptan tablets or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7) ].

Pregnancy

Advise patients to notify their healthcare provider if they are pregnant or plan to become pregnant.

Lactation

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].

Revised: 10/2019

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