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PRODUCT: Relistor

COMPANY: Wyeth

PHARMACOLOGIC CLASS: Opioid antagonist (peripheral)

ACTIVE INGREDIENTS: Methylnaltrexone bromide 12mg/0.6mL; soln for SC inj.

INDICATION: Opioid-induced constipation.

PHARMACOLOGY: The use of opioid analgesics can lead to constipation due to their effect on intestinal smooth muscle and their interference with normal bowel elimination function. Methylnaltrexone bromide is a mu-opioid receptor antagonist that has limited ability to cross the blood-brain barrier. It blocks the effects of opioids in peripheral tissues, including the GI tract, mitigating their constipating effects without interfering with their centrally-mediated analgesia.

CLINICAL TRIALS: The results of two placebo-controlled studies demonstrated the efficacy and safety of Relistor in treating opioid-induced constipation. The studies involved 287 patients with advanced illness (eg, incurable cancer, end-stage COPD, heart failure, Alzheimer’s disease, AIDS). Before screening, patients had been receiving palliative opioid therapy and had opioid-induced constipation. They were on a stable opioid regimen for at least 3 days before randomization. The first study compared single doses of the study drug (0.15mg/kg or 0.3mg/kg) to placebo in a double-blind phase that was followed by an open-label 4-week period in which Relistor was used as needed. The primary endpoint was the proportion of patients with rescue-free laxation within 4 hours of the double-blind dose of the study drug. Patients given either dose of Relistor had a significantly higher rate of laxation than those given placebo.

In the second trial, either the study drug or placebo was given every other day for 2 weeks. During the first week, patients received either Relistor 0.15mg/kg or placebo. In the second week, the dose could be increased to 0.3mg/kg if needed (≤2 rescue-free laxations up to day 8). Patients given the study drug had a higher rate of laxation within 4 hours of the first dose than those given placebo, and they had significantly higher rates of laxation within 4 hours after at least two of the first four doses. The laxation response rate was shown to be consistent from the first dose to the 7th dose over the 2-week period.

There was no relationship seen between baseline opioid doses and the laxation response in patients given Relistor. Daily opioid use did not change substantially in either the patients given the study drug or those given placebo, and there was no relevant changes in pain scores from baseline between the groups. Open-label extension studies indicate that the drug maintains its effectiveness for up to 4 months of treatment.

ADULTS: Give by SC injection in upper arm, abdomen, or thigh once every other day as needed (max 1 dose/24hrs); rotate injection sites. <38kg or >114kg: 0.15mg/kg. 38– <62kg: 8mg. 62–114kg: 12mg. Severe renal impairment (CrCl<30mL/min): reduce dose by 1/2.

CHILDREN: Not recommended.

CONTRAINDICATIONS: Mechanical GI obstruction (known or suspected).

PRECAUTIONS: Reevaluate if severe or persistent diarrhea occurs. Peritoneal catheterization. Bowel movement may occur within 30min of dosing. Pregnancy (Cat.B). Nursing mothers.

ADVERSE REACTIONS: Abdominal pain, flatulence, nausea, dizziness, diarrhea.

HOW SUPPLIED: Single-use vial—1 Kit (w. 7 vials, syringes, needles, supplies)—1

Facts about opioid-induced constipation

• Constipation is the most frequent adverse effect in patients receiving long-term opioid therapy. Clinicians should consider prophylactic therapy when starting patients on opioids, although common approaches such as fiber, fluids, and exercise may not be adequate for very ill patients who are receiving palliative care.

• Agents such as docusate, a stool softener, and bulk-forming laxatives are likely to be ineffective, or ineffective when used alone. Patients undergoing palliative care may have trouble ingesting enough fluids for these agents to work well.

• More effective agents include osmotic laxatives such as mannitol, lactulose, and sorbitol; magnesium hydroxide and magnesium sulfate; stimulant laxatives such as senna and bisacodyl; suppositories and enemas; and opioid antagonists.

• In addition to methylnaltrexone (Relistor), other opioid antagonists that may be prescribed for opioid-induced constipation include naloxone and nalmefene.

Data from Herndon CM, Jackson KC, Hallin PA. Management of opioid-induced gastrointestinal effects in patients receiving palliative care. Medscape. www.medscape.com/viewarticle/427442_1. Accessed July 11, 2008.

PRODUCT: Treximet

COMPANY: GlaxoSmithKline

PHARMACOLOGIC CLASS: Antimigraine (Selective 5-HT1B/1D receptor agonist + NSAID)

ACTIVE INGREDIENTS: Sumatriptan (as succinate) 85mg, naproxen sodium 500mg; tabs.

INDICATION: Acute treatment of migraine.

PHARMACOLOGY: Treximet is a combination product that treats migraine headaches via multiple mechanisms: sumatriptan selectively vasoconstricts intracranial/extracerebral blood vessels and inhibits trigeminal sensory nerve activation and the release of vasoactive neuropeptides, while naproxen inhibits the production of prostaglandin mediators of inflammation.

CLINICAL TRIALS: The efficacy of Treximet was established in two randomized, double-blind, multicenter, parallel-group studies which used placebo, sumatriptan, and naproxen sodium as comparison treatments.

ADULTS: Swallow whole. 1 tab once; may repeat once after 2 hours; max 2 tabs/day. The safety of treating an average of more than 5 migraines in a 30-day period has not been established.

CHILDREN: Not recommended.

CONTRAINDICATIONS: Aspirin allergy or triad syndrome (asthma, rhinitis, nasal polyps), hypotension with prior NSAID or aspirin use. History, symptoms, or signs of ischemic cardiac (eg, MI, angina pectoris, silent myocardial ischemia), cerebrovascular (eg, stroke, TIA), or peripheral vascular (eg, ischemic bowel disease, Raynaud) syndromes. Vasospastic coronary artery disease (CAD). Uncontrolled hypertension (HTN). Significant underlying cardiovascular disease. Basilar or hemiplegic migraine. Coronary artery bypass surgery. Hepatic impairment (esp. elderly). Within 24 hrs of ergot-type drugs (eg, methysergide, dihydroergotamine) or other 5-HT1 agonists. During or within 2 weeks after discontinuing MAO- type A inhibitors. 3rd trimester pregnancy.

PRECAUTIONS: Confirm diagnosis. Avoid excessive use. Likelihood of unrecognized coronary artery disease (HTN, hypercholesterolemia, men over age 40, postmenopausal women, obese, smokers, diabetes, strong family history): not recommended; exclude underlying cardiovascular disease, supervise 1st dose, consider monitoring ECG. Active peptic ulcer. History of GI disease or bleeding disorders. Monitor for GI bleed. Severe renal dysfunction (CrCl<30mL/min): not recommended. Impaired renal or hepatic function. Anemia. Asthma. Heart failure. Edema. Dehydration. HTN. Seizure disorders. Elderly. Debilitated. Pregnancy (Cat.C; see Contraindications). Labor & delivery, nursing mothers: not recommended.

INTERACTIONS: Ergotamines, other 5-HT1 agonists, MAOIs: see Contraindications. Avoid aspirin, other NSAIDs. Serotonin syndrome with SSRIs (eg, citalopram, fluoxetine), SNRIs (eg, duloxetine, venlafaxine). May potentiate methotrexate, lithium. May antagonize diuretics, antihypertensives (eg, ß-blockers). Increased risk of renal toxicity with ACEIs, diuretics. Increased risk of GI bleed with oral corticosteroids, anticoagulants (monitor), alcohol. Probenecid increases naproxen levels and delays elimination. May interfere with tests for 17-ketogenic steroids, 5-HIAA.

ADVERSE REACTIONS: Dizziness, somnolence, paresthesia, nausea, dyspepsia, dry mouth, GI ulcers/bleed, abdominal pain, chest or neck/throat/ jaw discomfort/pain, fatigue.

NOTE: Register pregnant patients exposed to Treximet by calling (800) 336-2176.

HOW SUPPLIED: Tabs—9 (blister card)

Facts about migraine

• Nearly 30 million Americans suffer from migraine, with women being affected three times more often than men. Migraines are most frequent in people aged 15 to 55 years, and 70% to 80% of those with migraine have a positive family history.

• Fewer than 50% of migraineurs have received an accurate diagnosis.

• Migraine triggers include alteration of the sleep-wake cycle; missed or delayed meals; certain medications; bright lights, sunlight, fluorescent lights, TV and movie viewing; certain foods; and excessive noise. Stress and underlying depression can also trigger migraines.

• Migraine may cause pain on one side of the head, pulsating or throbbing pain, moderate to intense pain that affects daily activities, nausea and vomiting, photophobia, audiophobia, and visual disturbances or aura. Attacks can last up to 72 hours, sometimes longer, and exertion may make the migraine worse.

• Migraine is diagnosed primarily through the history. The patient reports classic migraine symptoms; plus, there may be a family history of similar headaches. The physical examination of a patient who is not having a migraine will be unrevealing. Imaging studies may be helpful to rule out organic causes for the headaches. No test is currently available to confirm the diagnosis of migraine.

Data from Migraine. National Headache Foundation Web site. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed July 11, 2008.

PRODUCT: Patanase

COMPANY: Alcon

PHARMACOLOGIC CLASS: Antihistamine (H1-blocker)

ACTIVE INGREDIENTS: Olopatadine (as HCl) 0.6% (665mcg/spray); aqueous nasal spray; contains benzalkonium chloride.

INDICATION: Seasonal allergic rhinitis.

PHARMACOLOGY: Seasonal allergic rhinitis describes an array of symptoms such as congestion, sneezing, itchy nose, and rhinorrhea caused by a sensitivity to seasonal pollens. Olopatadine is an antihistamine that relieves these symptoms by interfering with the inflammatory response to the allergens. This nasal spray formulation of the drug enables the patient to directly target the area of the inflammatory symptoms.

CLINICAL TRIALS: Three randomized, double-blind, placebo-controlled, parallel-group, multicenter, 2-week studies were conducted to establish the safety and efficacy of olopatadine nasal spray in the treatment of seasonal allergic rhinitis. In these studies, 1,598 adult and adolescent patients were treated with either olopatadine 0.4%, olopatadine 0.6%, or placebo (vehicle nasal spray). Efficacy was assessed by patient recordings of four separate nasal symptom scores (nasal congestion, rhinorrhea, itchy nose, and sneezing). Symptoms were recorded as reflective (symptom severity over the past 12 hours) or instantaneous (symptom severity at the time of recording) on a scale of 0 to 3 (absent, mild, moderate, or severe). The primary efficacy end point was the difference from placebo in the percentage change from baseline in the sum of AM and PM reflective total nasal symptoms scores, averaged over the 2-week period.

In each trial, patients treated with the study drug (two sprays in each nostril twice daily) had statistically significantly greater decreases in the reflective total nasal symptom score, compared to vehicle. For olopatadine 0.6%, the changes from baseline in the two studies were –3.63 and –2.90, respectively, compared to –2.67 and –1.92 for placebo.

The onset of action was assessed by an instantaneous recording of the total nasal symptom score twice daily after the first dose of study drug. Onset of action was apparent after 1 day of dosing.

In three environmental exposure single-dose studies, patients were exposed to high levels of pollen and then treated with either olopatadine nasal spray or placebo. They then recorded their allergy symptoms hourly as instantaneous scores for the next 12 hours. In these studies, olopatadine 0.6% nasal spray had an onset of action of 30 minutes post-dose.

ADULTS: 2 sprays in each nostril twice daily.

CHILDREN: Not recommended.

PRECAUTIONS: Other nasal diseases: not recommended. Avoid eyes. Monitor for nasal mucosal changes. Pregnancy (Cat.C). Nursing mothers.

Interactions: Potentiates CNS depression with alcohol, other CNS depressants.

ADVERSE REACTIONS: Bitter taste, headache, epistaxis, throat pain, post-nasal drip, cough, nasal ulceration, somnolence.

ADDITIONAL PATIENT INFORMATION: Prime pump before first use (5 sprays) and if not used for 7 days (2 sprays). Discard after 240 sprays have been dispensed.

HOW SUPPLIED: Nasal spray pump—30.5g (240 sprays)

Facts about seasonal allergic rhinitis

• About 40 million people in the United States suffer from allergic rhinitis. They may have associated disorders such as asthma, otitis media, Eustachian tube dysfunction, sinusitis, nasal polyps, allergic conjunctivitis, or atopic dermatitis.

• Quality of life can be significantly impaired in persons with allergic rhinitis. The sufferer may experience fatigue, drowsiness (due to the disease or to medications), and malaise that can negatively affect work and school performance, lead to missed days, and cause traffic accidents.

• The overall cost (direct and indirect) of allergic rhinitis was recently estimated to be $5.3 billion per year.

• Seasonal allergic rhinitis is commonly caused by allergy to seasonal pollens and outdoor molds.

• Tree pollens are most commonly present in the spring, whereas grass pollens are most predominant from late spring to early fall. Ragweed, a common cause of allergic rhinitis in much of the United States, is prominent in late summer and fall, but other weed pollens may be present year round.

• The presence of outdoor molds is variable according to climate, season, and geographic location.

• Treatments include allergen avoidance and environmental controls, pharmacotherapy, and immunotherapy.

Data from Sheikh J. Rhinitis, allergic. eMedicine Web site. www.emedicine.com/MED/topic104.htm. Accessed July 11, 2008.