Strattera

1 INDICATIONS AND USAGE STRATTERA is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients 6 years of age and older. STRATTERA is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with ADHD. STRATTERA ® is a selective norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of ADHD in adults and pediatric patients 6 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Prior to initiating treatment with STRATTERA, screen patients for a personal or family history of bipolar disorder, mania, or hypomania. ( 2.1 , 5.6 ) See table below for the recommended STRATTERA dosage. ( 2.3 ) 1 Administer either as once daily dosage in the morning or as evenly divided twice daily dosage in the morning and late afternoon/early evening. Age and Body Weight Starting Dosage Target Dosage 1 Maximum Total Daily Dose 1 Pediatrics who weigh less than 70 kg 0.5 mg/kg/day 1.2 mg/kg/day 1.4 mg/kg/day or 100 mg/day (whichever is less) Pediatrics who weigh 70 kg or more and adults 40 mg/day 80 mg/day 100 mg/day For the recommended dosage in patients with hepatic impairment, see Full Prescribing Information. ( 2.4 ) For the recommended dosage with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers, see Full Prescribing Information. ( 2.5 ) 2.1 Recommendations Prior to Initiating STRATTERA Treatment Prior to initiating treatment with STRATTERA, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.6 )]. 2.2 Administration Instructions STRATTERA may be taken with or without food. Take STRATTERA capsules whole; do not open the capsules. 2.3 Recommended Dosage Table 1 includes the recommended STRATTERA dosage in adult patients and pediatric patients 6 years of age and older for acute treatment of ADHD. Table 1: Recommended Dosage of STRATTERA for Acute Treatment of ADHD a Administer either as once daily dosage in the morning or as evenly divided twice daily dosage in the morning and late afternoon/early evening. b No additional benefit has been demonstrated with STRATTERA dosages higher than 1.2 mg/kg/day [see Clinical Studies ( 14 )] . c If a patient has not achieved an optimal response at 80 mg/day after 2 to 4 additional weeks, may increase the dosage to a maximum of 100 mg/day. There is no data that supports increased effectiveness at a dosage higher than 100 mg/day [see Clinical Studies ( 14 )] . Age and Body Weight Starting Dosage Titration Interval Target Dosage Maximum Dosage Pediatric patients who weigh less than 70 kg 0.5 mg/kg/day Minimum of 3 days 1.2 mg/kg/day a,b 1.4 mg/kg/day or 100 mg/day, whichever is less a Pediatric patients who weigh 70 kg or more and adult patients 40 mg/day Minimum of 3 days 80 mg/day a 100 mg/day a,c The health care provider who elects to use STRATTERA for extended periods should periodically reevaluate the long-term usefulness of STRATTERA for the individual patient. 2.4 Recommended Dosage in Patients with Hepatic Impairment For patients aged 6 years of age or older with: Severe hepatic impairment (HI) (Child-Pugh Class C), the recommended initial and target STRATTERA dosage is 25% of recommended dosage in patients with normal hepatic function [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] . Moderate HI (Child-Pugh Class B), the recommended initial and target STRATTERA dosage is 50% of the recommended dosage in patients with normal hepatic function [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] . Mild HI (Child-Pugh Class A), the recommended initial and target STRATTERA dosage is the same as those with normal hepatic function. 2.5 Recommended Dosage with Concomitant Use of Strong CYP2D6 Inhibitors or in CYP2D6 Poor Metabolizers Consider genetic testing to determine the patient's CYP2D6 metabolizer status. In patients taking a concomitant strong CYP2D6 inhibitor or who are CYP2D6 poor metabolizers, a longer titration interval of 4 weeks is recommended, if ADHD symptoms fail to improve and the initial STRATTERA dosage is well tolerated. The recommended starting, target, and maximum STRATTERA dosages are the same as outlined in Table 1 [ see Dosage and Administration ( 2.3 ) ]. For other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate), follow the recommended dosage, including the recommended titration interval (minimum of 3 days), as outlined in Table 1 [see Dosage and Administration ( 2.3 )]. 2.6 Switching to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of STRATTERA. In addition, at least 14 days must elapse after stopping STRATTERA before starting an MAOI antidepressant. 2.7 Recommendations for a Missed Dose If a STRATTERA dose is missed, take the dose as soon as possible, but do not take more than the prescribed total daily amount of STRATTERA in any 24-hour period. 2.8 Recommendations for Discontinuation When discontinuing STRATTERA, no taper is needed [see Drug Abuse and Dependence ( 9.2 , 9.3 )].

6 ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice the incidence of placebo patients): Pediatric Clinical Studies: Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. ( 6.1 ) Adult Clinical Studies: Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. ( 6.1 ) Patients should be instructed to use caution when driving a car or operating hazardous machinery (because of somnolence) until they are reasonably certain that their performance is not affected by STRATTERA. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. STRATTERA was administered to 5,382 pediatric patients 6 years of age and older in clinical ADHD studies (Studies 1, 2, 3, 4, and 5) [see Clinical Studies ( 14.1 )] and 1,007 adults in clinical ADHD studies (Studies 6 and 7) [see Clinical Studies ( 14.2 )] . In the ADHD clinical trials, 2,529 pediatric patients were treated for over 6 months which included 1,625 pediatric patients who were treated for longer than 1 year. Adverse Reactions in the Clinical Trials of Pediatric Patients 6 Years of Age and Older with ADHD Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: In the acute placebo-controlled studies of pediatric patients 6 years of age and older with ADHD, 3% (48/1,613) of STRATTERA-treated pediatric patients and 1.4% (13/945) of placebo-treated pediatric patients discontinued due to an adverse reaction. Among STRATTERA-treated patients, irritability (0.3%, N=5); somnolence (0.3%, N=5); aggression (0.2%, N=4); nausea (0.2%, N=4); vomiting (0.2%, N=4); abdominal pain (0.2%, N=4); constipation (0.1%, N=2); fatigue (0.1%, N=2); feeling abnormal (0.1%, N=2); and headache (0.1%, N=2) were the reasons for discontinuation reported by more than one patient. For all studies, (including open-label and long-term studies), 6% of STRATTERA-treated pediatric patients who were other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and 11% of those who were CYP2D6 poor metabolizers discontinued due to an adverse reaction. Common Adverse Reactions in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: Common adverse reactions (incidence of 2% or greater in STRATTERA-treated patients and with a higher incidence in STRATTERA-treated patients compared to placebo-treated patients) in pediatric patients 6 years of age and older with ADHD are listed in Table 2 . The most commonly observed adverse reactions in STRATTERA-treated patients (incidence of ≥5% and ≥ twice the incidence in placebo-treated patients), for either twice daily or once daily dosing were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence ( see Tables 2 and 3 ). Table 2: Common Adverse Reactions a in Acute Studies (up to 18 weeks) in Pediatric Patients 6 Years and Older with ADHD a Adverse reactions reported by at least 2% of STRATTERA-treated patients and greater than placebo-treated patients. b Abdominal pain includes the terms: upper abdominal pain, and epigastric discomfort. c Somnolence includes the term sedation. Adverse Reaction STRATTERA (N=1,597) Placebo (N=934) Headache 19% 15% Abdominal pain b 18% 10% Decreased appetite 16% 4% Somnolence c 11% 4% Vomiting 11% 6% Nausea 10% 5% Fatigue 8% 3% Irritability 6% 3% Dizziness 5% 2% Decreased weight 3% 0% Anorexia 3% 1% Rash 2% 1% Adverse reaction in the STRATTERA-treated patients who received twice daily, and once daily dosing are shown in Table 3 (adverse reactions based on statistically significant Breslow-Day tests). Table 3: Common Adverse Reactions in Acute Studies (up to 18 weeks) in Pediatric Patients 6 Years and Older with ADHD a Abdominal pain included the terms: upper abdominal pain, and epigastric discomfort. b Mood swings didn't meet the statistical significance on Breslow-Day test at 0.05 level, but p-value was <0.1 (trend). c Constipation didn't meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility. Adverse Reaction ADHD Studies with Twice Daily Dosing ADHD Studies with Once Daily Dosing STRATTERA (N=715) Placebo (N=434) STRATTERA (N=882) Placebo (N=500) Abdominal pain a 17% 13% 18% 7% Vomiting 11% 8% 11% 4% Nausea 7% 6% 13% 4% Fatigue 6% 4% 9% 2% Mood swings b 2% 0% 1% 1% Constipation c 2% 1% 1% 0% Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: Table 4 displays adverse reactions that occurred in at least 2% of STRATTERA-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate). Table 4: Common Adverse Reactions a in STRATTERA-treated Pediatric Patients 6 Years and Older with ADHD by CYP2D6 Metabolizer Types a Adverse reactions that occurred in at least 2% of STRATTERA-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate). b Depression included the following terms: major depression, depressive symptoms, depressed mood, dysphoria. Adverse Reaction STRATTERA CYP2D6 Poor Metabolizers (N=355) STRATTERA Other CYP2D6 Metabolizer Types (N=5,019) Insomnia 11% 6% Decreased weight 7% 4% Constipation 7% 4% Depression b 7% 4% Tremor 5% 1% Excoriation 4% 2% Sedation 4% 2% Middle insomnia 3% 1% Conjunctivitis 3% 1% Syncope 3% 1% Early morning awakening 2% 1% Mydriasis 2% 1% Less Common Adverse Reactions in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERA treatment: blood pressure increased, early morning awakening (terminal insomnia), flushing, mydriasis, sinus tachycardia, asthenia, palpitations, mood swings, constipation, and dyspepsia. The following reactions were reported by at least 2% of patients treated with STRATTERA, and equal to or less than placebo: pharyngolaryngeal pain, insomnia (insomnia includes the terms, insomnia, initial insomnia, middle insomnia). The following reaction did not meet this criterion but shows a statistically significant dose relationship: pruritus. Seizures in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: STRATTERA has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from STRATTERA studies. In the clinical development program, seizures were reported in 0.2% (12/5,073) of STRATTERA-treated pediatric patients whose average age was 10 years old (range 6 to 16 years of age). In these clinical trials, the seizure incidence among CYP2D6 poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4,741) for other CYP2D6 metabolizer types. Heart Rate and Blood Pressure Increases in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of pediatric patients experienced potentially clinically important changes in heart rate (≥20 beats per minute) or blood pressure (≥15 to 20 mm Hg) [see Contraindications ( 4 ) and Warnings and Precautions ( 5.4 )] . Adverse Reactions in the Clinical Trials of Adults with ADHD Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Adults: In the acute adult placebo-controlled trials, 11.3% (61/541) STRATTERA-treated patients and 3% (12/405) placebo-treated patients discontinued for adverse reactions. Among STRATTERA-treated patients, insomnia (0.9%, N=5); nausea (0.9%, N=5); chest pain (0.6%, N=3); fatigue (0.6%, N=3); anxiety (0.4%, N=2); erectile dysfunction (0.4%, N=2); mood swings (0.4%, N=2); nervousness (0.4%, N=2); palpitations (0.4%, N=2); and urinary retention (0.4%, N=2) were the reasons for discontinuation reported by more than 1 patient. Common Adverse Reactions in the Clinical Studies of Adults: Commonly observed adverse reactions associated with the use of STRATTERA (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (STRATTERA incidence greater than placebo) are listed in Table 5 . The most commonly observed adverse reactions in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients) were: constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation ( see Table 5 ). Table 5: Common Adverse Reactions a Associated in Acute Studies (up to 25 weeks) of Adult Patients with ADHD a Reactions reported by at least 2% of patients treated with STRATTERA, and greater than placebo. The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERAtreatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention. b Insomnia includes the terms initial insomnia, middle insomnia, terminal insomnia and other related terms. c Based on total number of males (STRATTERA group, N=943; placebo group, N=869). d Somnolence includes related terms. e Abdominal pain includes the terms: upper abdominal pain and other related terms. f Urinary hesitation includes the term decreased urine flow. g Based on total number of females (STRATTERA, N=754; placebo, N=691). Adverse Reaction STRATTERA (N=1,697) Placebo (N=1,560) Nausea 26% 6% Dry mouth 20% 5% Decreased appetite 16% 3% Insomnia b 15% 8% Fatigue 10% 6% Erectile dysfunction c 8% 1% Constipation 8% 3% Dizziness 8% 3% Somnolence d 8% 5% Abdominal pain e 7% 4% Urinary hesitation f 6% 1% Irritability 5% 3% Ejaculation delayed c and/or ejaculation disorder c 4% 1% Hyperhidrosis 4% 1% Dyspepsia 4% 2% Vomiting 4% 2% Abnormal dreams 4% 3% Chills 3% 0% Paraesthesia 3% 0% Hot flush 3% 0% Palpitations 3% 1% Libido decreased 3% 1% Sleep disorder 3% 1% Dysmenorrhea g 3% 2% Dysuria 2% 0% Thirst 2% 1% Weight decreased 2% 1% Feeling jittery 2% 1% Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Adults: Table 6 displays adverse reactions that occurred in at least 2% of STRATTERA-treated adult patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent compared to other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate). Table 6: Common Adverse Reactions a in STRATTERA-treated Adult Patients with ADHD by CYP2D6 Metabolizer Types a Adverse reactions that occurred in at least 2% of STRATTERA-treated adult patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate). Adverse Reaction STRATTERA CYP2D6 Poor Metabolizers (N=203) STRATTERA Other CYP2D6 Metabolizer Types (N=3,599) Dry mouth 35% 17% Decreased appetite 23% 15% Erectile dysfunction 21% 9% Insomnia 19% 11% Hyperhidrosis 15% 7% Constipation 11% 7% Sleep disorder 7% 3% Urinary retention 6% 1% Ejaculation disorder 6% 2% Tremor 5% 1% Feeling jittery 5% 2% Middle insomnia 5% 3% Blurred vision 4% 1% Terminal insomnia 3% 1% Peripheral coldness 3% 1% Less Common Adverse Reactions in the Clinical Studies of Adults: The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERA treatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention. Seizures in the Clinical Studies of Adults: STRATTERA has not been systematically evaluated in adult patients with a seizure disorder as these patients were excluded from clinical studies during the product's premarket testing. In the clinical development program, seizures were reported on 0.1% (1/748) of adult patients. In these clinical trials, no CYP2D6 poor metabolizers (0/43) reported seizures compared to 0.1% (1/705) for other CYP2D6 metabolizer types. Heart Rate and Blood Pressure Increases in the Clinical Studies of Adults: Table 7 displays the proportion of STRATTERA-treated and placebo-treated patients who had an increase in diastolic blood pressure (DBP) ≥15 mm Hg, systolic blood pressure (SBP) ≥20 mm Hg, or heart rate ≥ 20 bpm in short-term, placebo-controlled clinical studies in pediatric and adult patients with ADHD [see Warnings and Precautions ( 5.4 )]. Table 7: Proportion of ADHD Patients With an Increase of ≥ 15 mm Hg in DBP, ≥20 mm Hg in SBP, or ≥ 20 bpm in Heart Rate a a Abbreviations: bpm=beats per minute; DBP=diastolic blood pressure; HR=heart rate; mm Hg=millimeters mercury; SBP=systolic blood pressure. b Proportion of patients meeting threshold at any one time during the clinical studies. Pediatric Acute ADHD Studies Adult Acute ADHD Studies Maximum b Endpoint Maximum b Endpoint STRATTERA Placebo STRATTERA Placebo STRATTERA Placebo STRATTERA Placebo DBP (≥15 mm Hg) 22% 14% 9% 5% 13% 9% 5% 4% SBP (≥20 mm Hg) 13% 9% 5% 3% 12% 8% 4% 3% HR (≥20 bpm) 23% 12% 12% 4% 22% 8% 10% 2% Additional data from ADHD clinical trials (controlled and uncontrolled) showed that approximately 5 to 10% of adult patients had potentially clinically important changes in heart rate (≥20 beats per minute) or blood pressure (≥15 to 20 mm Hg) [see Contraindications ( 4 ) and Warnings and Precautions ( 5.4 )] . Male and Female Sexual Dysfunction in the Clinical Studies of Adults : STRATTERA impaired sexual function in some patients. Estimates of the incidence of untoward sexual experience and performance in these studies are likely to underestimate their actual incidence because patients and health care providers may be reluctant to discuss them. Table 5 displays the incidence of sexual adverse reactions (reported by at least 2% of STRATTERA-treated adult patients in the placebo-controlled studies of adults with ADHD (i.e., erectile dysfunction, dysmenorrhea, and ejaculation delayed and/or ejaculation disorder). There are no adequate and well-controlled studies examining sexual dysfunction with STRATTERA treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of STRATTERA, health care providers should routinely inquire about sexual dysfunction. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of STRATTERA. Unless otherwise specified, these adverse reactions have occurred in adults and pediatric patients. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular system: QT prolongation, syncope. Peripheral vascular effects: Raynaud's phenomenon. General disorders and administration site conditions: Lethargy. Musculoskeletal system: Rhabdomyolysis. Nervous system disorders: Hypoaesthesia; paraesthesia in pediatric patients; sensory disturbances; tics. Psychiatric disorders: Depression and depressed mood; anxiety, libido changes. Seizures: Seizures have been reported and included patients with pre-existing seizure disorders, those with identified risk factors for seizures, and patients with neither a history of nor identified risk factors for seizures. The exact relationship between STRATTERA and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients. Skin and subcutaneous tissue disorders: Alopecia, hyperhidrosis. Urogenital system: Male pelvic pain; urinary hesitation in pediatric patients; urinary retention in pediatric patients.

7 DRUG INTERACTIONS See Table 8 for clinically significant drug interactions with STRATTERA and other drugs. Table 8: Clinically Significant Drug Interactions with STRATTERA and Other Drugs Monoamine Oxidase Inhibitors (MAOIs) Prevention or Management STRATTERA is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue, or in patients who stopped an MAOI within 14 days. Mechanism and Clinical Effect(s) As with other drugs affecting brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (hyperthermia, rigidity, myoclonus, autonomic instability with fluctuations of vital signs, extreme agitation progressing to delirium/coma) with concomitant use of STRATTERA and an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Strong CYP2D6 Inhibitors Prevention or Management With concomitant use of STRATTERA and a strong CYP2D6 inhibitor, increase the titration interval [see Dosage and Administration ( 2.5 ) and Clinical Pharmacology ( 12.3 )]. Mechanism and Clinical Effect(s) Atomoxetine is a CYP2D6 substrate. The concomitant use of STRATTERA and a strong CYP2D6 inhibitor increases atomoxetine exposure [see Clinical Pharmacology ( 12.3 )] . Antihypertensive Drugs Prevention or Management Increase the frequency of monitoring blood pressure and adjust STRATTERA dosage as clinically appropriate. Mechanism and Clinical Effect(s) Because of increased risk of increased blood pressure, STRATTERA should be used cautiously with antihypertensive drugs, other drugs that increase blood pressure or pressor drugs (e.g., dopamine, dobutamine). Albuterol or Other Beta2 Agonists Prevention or Management Increase the frequency of monitoring blood pressure and heart rate and adjust STRATTERA dosage as clinically appropriate. Mechanism and Clinical Effect(s) Systemically administered albuterol (e.g., oral) can be potentiated by atomoxetine, resulting in increases in heart rate and blood pressure. [see Clinical Pharmacology ( 12.3 )]. Monoamine Oxidase Inhibitors: Concomitant use contraindicated. ( 4 , 7 ) Strong CYP2D6 Inhibitors: With concomitant use of STRATTERA and strong CYP2D6 inhibitors, increase the titration intervals. ( 7 ) Antihypertensives: Increase the frequency of monitoring blood pressure and adjust STRATTERA dosage as clinically appropriate. ( 7 ) Albuterol (or other beta2 agonists): Increase the frequency of monitoring blood pressure and heart rate. ( 7 )

16.2 Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].