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Patient (Naproxen (Pharmacokinetics (Excretion (Urine (95%; primarily as…

- - - - Capsules (Naproxen Sodium Oral)
        
        220 mg (per each): $0.34
      - Suspension (Naprosyn Oral)
        
        125 mg/5 mL (per mL): $2.66
      - Suspension (Naproxen Oral)
        
        125 mg/5 mL (per mL): $1.96
      - Tablet, 24-hour (Naprelan Oral)
        
        375 mg (per each): $26.14
        
        500 mg (per each): $23.94
        
        750 mg (per each): $27.71
      - Tablets (Naproxen Oral)
        
        250 mg (per each): $0.08 - $0.80
        
        375 mg (per each): $0.11 - $1.10
        
        500 mg (per each): $0.13 - $2.79
      - Tablets (Naproxen Sodium Oral)
        
        220 mg (per each): $0.08 - $0.11
        
        275 mg (per each): $2.29
        
        550 mg (per each): $3.56 - $3.57
  - - - Urine (95%; primarily as metabolites); feces (≤3%)
    - - Dosage expressed as naproxen base; 200 mg naproxen base is equivalent to 220 mg naproxen sodium. For relief of acute pain, naproxen sodium may be preferred due to more rapid absorption and onset; naproxen base may also be used however EC-Naprosyn is not recommended.
        
        Ankylosing spondylitis, osteoarthritis, rheumatoid arthritis
        
        Naproxen extended-release tablets: Initial: 750 to 1,000 mg once daily; in patients who require higher level of anti-inflammatory/analgesic activity and have tolerated lower doses, may temporarily increase to 1,500 mg once daily
        
        Rectal suppository [Canadian product]: Insert one 500 mg suppository into the rectum once daily (Note: Suppository may be used to substitute for one oral dose in patients receiving 1,000 mg naproxen daily).
        
        Oral: 500 to 1,000 mg daily in 2 divided doses; in patients who require higher level of anti-inflammatory/analgesic activity and have tolerated lower doses, may increase to 1,500 mg/day for limited time period (<6 months)
        
        Gout, acute flares (alternative agent)
        
        Oral: 500 mg twice daily; initiate within 24 to 48 hours of flare onset preferably; discontinue 2 to 3 days after resolution of clinical signs; usual duration: 5 to 7 days
        
        Immediate release: Initial: 750 mg followed by 250 mg every 8 hours
        
        Extended-release tablets: Initial: 1,000 to 1,500 mg once daily followed by 1,000 mg once daily. Note: Naproxen delayed-release tablets are not recommended because of the delay in absorption.
        
        Pain (mild to moderate), dysmenorrhea, acute tendonitis, bursitis
        
        Oral: Initial: 500 mg, followed by 500 mg every 12 hours or 250 mg every 6 to 8 hours; maximum daily dose: Day 1: 1,250 mg; subsequent daily doses should not exceed 1,000 mg
        
        Naproxen extended-release tablets: Oral: Initial: 1,000 mg once daily; may temporarily increase to 1,500 mg once daily if greater pain relief is needed. Dose should be subsequently reduced to a maximum of 1,000 mg daily.
        
        OTC labeling
        
        Pain, fever: 200 mg every 8 to 12 hours; if needed, may take 400 mg for the initial dose; maximum: 400 mg in any 8- to 12-hour period or 600 mg/24 hours
    - - Extensively metabolized in the liver to 6-0-desmethyl naproxen; parent drug and desmethyl metabolite undergo further metabolism to their respective acylglucuronide conjugated metabolites
    - - Analgesic: <12 hours
    - - Normal renal function: 12 to 17 hours; Moderate-to-severe renal impairment: ~15 to 21 hours
  - - - Risk Rating D: Consider therapy modification
      - Patient Management The concomitant use of herbs possessing anticoagulation/antiplatelet properties with other herbs or drugs possessing similar properties should be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. For patients scheduled for surgical, dental, or other invasive procedures, anticoagulant/antiplatelet herbs should be discontinued 2 weeks prior to the scheduled procedure.
- - - - Cancer chemotherapy-induced nausea and vomiting:
        
        IV: Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy (including high-dose cisplatin).
        
        Oral:
        
        Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy (including cisplatin ≥50 mg/m2).
        
        Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
      - Postoperative nausea and/or vomiting: IV, IM, Oral: Prevention of postoperative nausea and/or vomiting (PONV). If nausea/vomiting occur in a patient who had not received prophylactic ondansetron, IV ondansetron may be administered to prevent further episodes.
        
        Limitations of use: Routine prophylaxis for PONV in patients with minimal expectation of nausea and/or vomiting is not recommended, although use is recommended in patients when nausea and vomiting must be avoided in the postoperative period, even if the incidence of PONV is low.
      - Radiotherapy-associated nausea and vomiting: Oral: Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.
  - - - Adults: 3 to 6 hours
      - Mild-to-moderate hepatic impairment (Child-Pugh classes A and B): 12 hours
      - Severe hepatic impairment (Child-Pugh class C): 20 hours
    - - 2 to 7 hours
    - - Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation; CYP1A2, CYP2D6, and CYP3A4 substrate, some demethylation occurs
    - - Gastroparesis, symptomatic treatment of nausea and vomiting (alternative agent) : Note: For patients with persistent symptoms refractory to prokinetic therapy. No data available; recommendations for use and dose are based on expert opinion: Oral: 4 to 8 mg 3 times daily
      - Nausea and/or vomiting, acute, severe: Note: Use has primarily been evaluated in patients with undifferentiated nausea/vomiting presenting to the emergency department; however, clinical experience also suggests utility in nausea/vomiting due to viral gastroenteritis, acute mountain sickness, and a variety of other medical conditions associated with severe, self-limiting acute nausea/vomiting
    - - Urine (44% to 60% as metabolites, ~5% as unchanged drug); feces (~25%)
  - - - Solution (Ondansetron HCl Oral)
        
        4 mg/5 mL (per mL): $4.78 - $4.80
      - Tablet, orally-disintegrating (Ondansetron Oral)
        
        4 mg (per each): $22.25 - $23.11
        
        8 mg (per each): $36.66 - $38.50
      - Tablets (Ondansetron HCl Oral)
        
        4 mg (per each): $0.54 - $24.89
        
        8 mg (per each): $0.64 - $41.53
        
        24 mg (per each): $105.50 - $106.51
  - - - Risk Rating C: Monitor therapy
      - Patient Management The concomitant use of agents that enhance serotonin activity should be undertaken with caution due to the risk of serotonin syndrome. The labeling for 5HT3 antagonists warns of the risk of serotonin syndrome when 5HT3 antagonists are combined with other serotonergic medications and cautions that patients should be monitored for the development of serotonin syndrome during such therapy.
    - - Risk Rating B: No action needed
      - Patient Management No specific action is required, but be aware that acetaminophen may be less effective in patients treated with 5HT3 antagonists.
- - - - Capsules (Dicyclomine HCl Oral)
        
        10 mg (per each): $0.26 - $0.60
      - Solution (Bentyl Intramuscular)
        
        10 mg/mL (per mL): $50.44
      - Solution (Dicyclomine HCl Intramuscular)
        
        10 mg/mL (per mL): $24.38 - $50.40
      - Solution (Dicyclomine HCl Oral)
        
        10 mg/5 mL (per mL): $0.30
      - Tablets (Dicyclomine HCl Oral)
        
        20 mg (per each): $0.36 - $0.78
  - - - Urine (80%, small amounts as unchanged drug); feces (8%)
    - - Irritable bowel syndrome-associated abdominal pain: Oral: Initial: 20 mg up to 4 times daily; some experts recommend only administering as needed or in anticipation of a stressor that triggers abdominal pain; intended for short-term use; scheduled dosing for >2 weeks has not been studied
    - - None known.
    - - Up to 4 hours
    - - Initial phase: ~1.8 hours; Terminal phase: Undetermined, but somewhat longer than the initial phase
  - - - Risk Rating C: Monitor therapy
      - Patient Management Increase the monitoring for evidence of constipation and/or urinary retention in patients using this combination. Advise patients to promptly report signs or symptoms suggestive of such adverse effects. Consider means of preventing or treating these effects if or when they occur.
- - - - Urine (primarily as glucuronide metabolites); feces (as unchanged drug); Clearance: 0.7 L/minute
    - - Adults
        
        Jaw pain due to temporomandibular disorder, acute (off-label)
        
        Immediate release: Usual: 10 mg once daily administered 1 to 2 hours before bedtime
        
        Muscle spasm: Oral: Note: Do not use longer than 2 to 3 weeks.
        
        Immediate release: Initial: 5 mg 3 times daily; may increase up to 10 mg 3 times daily if needed
        
        Extended release: Usual: 15 mg once daily; some patients may require up to 30 mg once daily
    - - Hepatic via CYP3A4, 1A2, and 2D6; may undergo enterohepatic recirculation
    - - Immediate release: 12 to 24 hours
    - - Normal hepatic function: Range: 8 to 37 hours; Immediate release: 18 hours; Extended release: 32 hours; Impaired hepatic function: 46.2 hours (range: 22.4 to 188 hours)
  - - - 7.5 mg (per each): $8.32
    - - 10 mg (per each): $0.07 - $2.98
      - 7.5 mg (per each): $4.81
      - 5 mg (per each): $0.07 - $1.73
    - - 30 mg (per each): $39.71 - $45.28
      - 15 mg (per each): $39.71 - $45.28
    - - 30 mg (per each): $47.66
      - 15 mg (per each): $47.66
  - - - Risk Rating C: Monitor therapy
      - The concomitant use of two or more drugs that have anticholinergic activity (either as a therapeutic intention or a side effect) is often clinically appropriate. However, it is important to recognize that the risk of unwanted effects may increase with such use. Monitor for additive anticholinergic effects if two or more of these agents are concomitantly used.
- - - - Hydrocodone: ~4 hours
    - - 4 to 8 hours
    - - Hydrocodone: Hepatic; O-demethylation via primarily CYP2D6 to hydromorphone (major, active metabolite with ~10- to 33-fold higher or as much as a >100-fold higher binding affinity for the mu-opioid receptor than hydrocodone); N-demethylation via CYP3A4 to norhydrocodone (major metabolite); and ~40% of metabolism/clearance occurs via other non-CYP pathways, including 6-ketosteroid reduction to 6-alpha-hydrocol and 6-beta-hydrocol, and other elimination pathways
    - - Norco:
        
        Hydrocodone bitartrate 5 mg and acetaminophen 325 mg
        
        Hydrocodone bitartrate 7.5 mg and acetaminophen 325 mg
        
        Hydrocodone bitartrate 10 mg and acetaminophen 325 mg
    - - Hydrocodone: Urine (26% of single dose in 72 hours, with ~12% as unchanged drug, 5% as norhydrocodone, 4% as conjugated hydrocodone, 3% as 6-hydrocodol, and 0.21% as conjugated 6-hydromorphol
  - - - 5-325 mg (per each): $3.55
      - 7.5-325 mg (per each): $4.13
      - 10-325 mg (per each): $5.72
  - - - Severity Major
        
        Reliability Rating Fair
        
        Risk Rating D: Consider therapy modification
      - Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. This recommendation comes specifically from the prescribing information for the Zohydro ER brand of extended-release hydrocodone but is likely reasonable for other hydrocodone-containing products as well. Warn patients and caregivers about the risk of slowed or difficult breathing and/or sedation and monitor patients closely for evidence of excessive CNS depression.
- - - - Tablet, 12-hour (buPROPion HCl ER (SR) Oral)
        
        100 mg (per each): $1.69 - $1.94
        
        150 mg (per each): $0.70 - $1.94
        
        200 mg (per each): $3.38 - $3.83
  - - - Urine (87%, primarily as metabolites); feces (10%, primarily as metabolites)
    - - Note: Bupropion is available as hydrochloride and hydrobromide salts. Doses are expressed in this monograph as hydrochloride salt except where noted as bupropion hydrobromide salt. Bupropion hydrochloride 150 mg is equivalent to about 174 mg of bupropion hydrobromide. Bupropion is available as immediate release, 12-hour extended release (sustained release), and 24-hour extended release tablets
        
        Attention-deficit/hyperactivity disorder (off-label use): Note: For patients with comorbid mood disorders or as an alternative agent for patients with substance use disorders.
        
        12-hour extended release (sustained release): Oral: Initial: 100 mg once daily in the morning; increase in 100 mg/day increments at intervals of 3 to 4 weeks based on response and tolerability up to 200 mg twice daily.
        
        24-hour extended release: Oral: Initial: 150 mg once daily in the morning for 1 week; increase to 300 mg once daily for 3 weeks; may further increase dose based on response and tolerability up to 450 mg once daily.
        
        Bipolar depression (off-label use): 12-hour extended release (sustained release): Oral: Initial: 100 mg once daily as an adjunct to mood stabilizer; increase based on response and tolerability at 2-week intervals up to 450 mg/day in 2 divided doses (average dose in clinical trials was 250 mg/day).
        
        Major depressive disorder (unipolar): Note: Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used. Slower dose titrations may be indicated based on patient care setting, symptom severity, and concern for side effects. May also be used as an alternative agent for patients with SSRI-induced sexual dysfunction.
        
        Immediate release: Oral: Initial: 100 mg twice daily; after 3 days may increase to the usual dose of 100 mg 3 times a day; if no clinical improvement after several weeks, may increase to a maximum dose of 450 mg/day in 3 or 4 divided doses; do not exceed 150 mg in a single dose.
        
        12-hour extended release (sustained release): Oral: Initial: 150 mg daily in the morning; if tolerated, after 3 days, may increase to a target dose of 150 mg twice daily; if no clinical improvement after several weeks, may increase to a maximum dose of 200 mg twice daily; do not exceed 200 mg in a single dose.
        
        24-hour extended release: Oral:
        
        Hydrochloride salt: Initial: 150 mg once daily in the morning; if tolerated, may increase as early as day 4 of dosing to 300 mg once daily; if no clinical improvement after 2 weeks, may increase to 450 mg once daily.
        
        Hydrobromide salt: Initial: 174 mg once daily in the morning; may increase as early as day 4 of dosing to 348 mg once daily (target dose).
        
        Seasonal affective disorder (SAD): 24-hour extended release: Oral:
        
        Hydrochloride salt: Initial: 150 mg once daily in the morning; if tolerated, may increase after 7 days to 300 mg once daily in the morning.
        
        Hydrobromide salt: Initial: 174 mg once daily in the morning; if tolerated, may increase after 7 days to 348 mg once daily in the morning.
        
        Selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction, augmentation (off-label use): 12-hour extended release (sustained release): Oral: Initial: 150 mg once daily for the first 3 days; increase to 150 mg twice daily, based on response and tolerability.
        
        Smoking cessation: Note: May be used as monotherapy or in combination with nicotine replacement therapy (Siu 2015): 12-hour extended release (sustained release): Oral: Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily (maximum dose: 300 mg/day). For patients who do not tolerate titration to the full dose, consider continuing 150 mg once daily; the lower dose has shown efficacy.
        
        MAOI recommendations: Switching to or from an MAOI antidepressant:
        
        Allow 14 days to elapse between discontinuing an MAOI intended to treat depression and initiation of bupropion.
        
        Allow 14 days to elapse between discontinuing bupropion and initiation of an MAOI intended to treat depression.
        
        Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose (eg, over 2 to 4 weeks) to allow for the detection of reemerging symptoms. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity.
    - - Extensively hepatic via CYP2B6 to hydroxybupropion; non-CYP-mediated metabolism to erythrohydrobupropion and threohydrobupropion. Metabolite activity ranges from 20% to 50% potency of bupropion.
    - - 1 to 2 days
    - - Elimination:
        
        Hydrobromide salt: 21 ± 7 hours; Metabolites: Hydroxybupropion: 24 ± 5 hours; Erythrohydrobupropion: 31 ± 8 hours; Threohydrobupropion: 51 ± 9 hours
        
        Hydrochloride salt: ~21 hours after chronic dosing (± 9 hours); Metabolites (after a single dose): Hydroxybupropion: 20 ± 5 hours; Erythrohydrobupropion: 33 ± 10 hours; Threohydrobupropion: 37 ± 13 hours
        
        Distribution: 3 to 4 hours
  - - - Major depressive disorder (unipolar [excluding Zyban]): Treatment of major depressive disorder (MDD)
      - Seasonal affective disorder (24-hour extended release [Aplenzin, Wellbutrin XL]): Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD)
      - Smoking cessation (12-hour extended release [sustained release; Zyban]): As an aid to smoking cessation treatment
  - - - Additional drug/group (CYP3A4 Inhibitors): The significance of this interaction may be greater in patients who are also receiving a CYP3A4 inhibitor or with use of a strong CYP2D6 inhibitor that also inhibits CYP3A4 (e.g., delaviridine, paroxetine, lopinavir, ritonavir, quinidine, or stiripentol).
      - Risk Rating C: Monitor therapy
      - CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Severity Moderate Reliability Rating Fair
      - Monitor patients closely for evidence of reduced analgesic response if using hydrocodone together with a strong CYP2D6 inhibitor. Patients using a CYP2D6 inhibitor that is also an inhibitor of CYP3A4 (e.g., delavirdine, lopinavir, paroxetine, ritonavir, quinidine, stiripentol) may experience greater hydrocodone concentrations and enhanced opioid effects.
- - - - Erosive esophagitis associated with gastroesophageal reflux disease: Short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis in adults and pediatric patients 5 years and older.
      - Maintenance of healing of erosive esophagitis: Maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gastroesophageal reflux disease (GERD).
      - Pathological hypersecretory conditions, including Zollinger-Ellison syndrome: Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.
    - - Pathological hypersecretory conditions, including Zollinger-Ellison: Treatment of adult patients with pathological hypersecretory conditions, including Zollinger-Ellison syndrome.
      - Gastroesophageal reflux disease associated with a history of erosive esophagitis: Short-term treatment (7 to 10 days) of adult patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis.
  - - - Oral, IV: 24 hours
    - - Extensively hepatic; CYP2C19 (demethylation), CYP3A4; no evidence that metabolites have pharmacologic activity
    - - Erosive esophagitis associated with GERD
        
        Oral
        
        Treatment: 40 mg once daily for up to 8 weeks; an additional 8 weeks may be used in patients who have not healed after an 8-week course. Lower doses (20 mg once daily) have been used successfully in mild GERD treatment.
        
        Maintenance of healing: 40 mg once daily; 20 mg once daily has been used successfully in maintenance of healing. Note: Has not been studied beyond 12 months.
        
        IV
        
        40 mg once daily for 7 to 10 days
      - Pathological hypersecretory conditions, including Zollinger-Ellison syndrome:
        
        Oral: Initial: 40 mg twice daily; adjust dose based on patient needs; doses up to 240 mg daily have been administered
        
        IV: 80 mg every 12 hours; adjust dose based on acid output measurements; 160 to 240 mg daily in divided doses has been used for a limited period (up to 7 days)
    - - Urine (71% as metabolites); feces (18%); pantoprazole clearance increased with weight and age
    - - Adults: 1 hour; increased to 3.5 to 10 hours with CYP2C19 deficiency
      - Children and Adolescents: IV (2 to 16 years of age): 1.22 ± 0.68 hours; Oral (5 to 16 years of age): 1.27 ± 1.29 hours
      - Neonates (PMA: 37 to 44 weeks): ~3 hours (Ward 2010)
  - - - 40 mg (per each): $18.07
    - - 40 mg (per each): $4.08 - $8.50
    - - 40 mg (per each): $6.00
    - - 20 mg (per each): $0.43 - $10.79
      - 40 mg (per each): $0.43 - $10.79
    - - 20 mg (per each): $18.08
      - 40 mg (per each): $18.08
- - - - 72 mcg (per each): $16.95
      - 145 mcg (per each): $16.95
      - 290 mcg (per each): $16.95
  - - - Primarily feces (3% to 5%; as the active metabolite)
    - - Chronic idiopathic constipation (CIC): Oral: 145 mcg once daily; 72 mcg once daily may be used based on patient presentation or tolerability.
      - Irritable bowel syndrome with constipation (IBS-C): Oral: 290 mcg once daily.
    - - Metabolized within GI tract to active metabolite; parent drug and metabolite undergo proteolytic degradation within the intestinal lumen to smaller peptides and amino acids
    - - Completely degraded within 30 minutes
    - - 3 minutes
  - - - Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to linaclotide or any component of the formulation