Craig I. Coleman, PharmD

In clinical trials of lorcaserin lasting at least 1 year, the most common adverse reactions occurring in >5% of patients without type 2 diabetes were headache, dizziness, fatigue, nausea, dry mouth, and constipation. In patients with type 2 diabetes, the most common adverse reactions were hypoglycemia, headache, back pain, cough, and fatigue. Other safety concerns included serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions, hypoglycemia (due to weight loss in type 2 diabetes), valvular heart disease, cognitive impairment, psychiatric disorders (i.e., euphoria, hallucination, and dissociation), heart rate decreases (of ~1.2 to 2.0 beats per minute), decreases in red and white blood cell counts, and priapism.   

The recommended dose of lorcaserin is 10 mg administered orally twice daily with or without food. Patients should be evaluated within 12 weeks for response; those who do not lose ≥5% of baseline body weight should discontinue lorcaserin. Due to the risk of serotonin syndrome or NMS-like reactions, coadministration of lorcaserin along with other serotonergic drugs (i.e., SSRIs, SNRIs, MAOIs, triptans, bupropion, dextromethorphan, and St. John's Wort, among others) should be undertaken with extreme caution.  

An estimated 33 million Americans suffer from overactive bladder (OAB). On June 28, 2012, FDA approved the beta-3 adrenergic agonist mirabegron (Myrbetriq) for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency. Mirabegron works by relaxing the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle. 

Mirabegron was evaluated in three 12-week, double-blind, randomized, placebo-controlled, multicenter clinical trials of overactive-bladder patients with symptoms of urge urinary incontinence, urgency, and urinary frequency. Results showed that mirabegron 25 mg and 50 mg statistically significantly reduced the number of times a patient had an incontinence episode (adjusted mean difference from placebo; -0.41 for 50 mg in study 1, -0.34 for 50 mg in study 2, and -0.40 to -0.42 for 25 mg and 50 mg, respectively, in study 3) and the number of times a patient urinated (adjusted mean difference from placebo; -0.60 for 50 mg in study 1, -0.61 for 50 mg in study 2, and -0.47 to -0.42 for 25 mg and 50 mg, respectively, in study 3) during a 24-hour period. 

The most common reported adverse reactions (occurring in >2% of subjects and more often than placebo) during the above-mentioned clinical trials of mirabegron were hypertension, nasopharyngitis, urinary tract infection, and headache. Mirabegron can increase blood pressure, and therefore, periodic blood pressure determinations are recommended (especially in hypertensive patients). Mirabegron is not recommended for use in patients with severe uncontrolled hypertension. A higher risk of urinary retention is present in patients suffering from bladder outlet obstruction or taking antimuscarinic drugs for OAB. 

The recommended starting dose of mirabegron is 25 mg once daily, with or without food. If the 25 mg dose is not effective within 8 weeks, the dose may be increased to 50 mg once daily. Patients with severe renal impairment (CrCl 15 to 29 mL/min) or moderate hepatic impairment (Child-Pugh Class B) should not receive doses >25 mg once daily. Mirabegron should not be administered to patients with end-stage renal disease or severe hepatic impairment. Mirabegron is a moderate CYP2D6 inhibitor and caution should be used when administering it concomitantly with drugs metabolized by CYP2D6 (i.e., metoprolol, despiramine, digoxin).   

 is associate professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn., and director of the Pharmacoeconomics and Outcomes Studies Group, Hartford Hospital.

Articles

FDA approves Lorcaserin and Mirabegron extended-release tablets.

New treatments for obesity and OAB

The short-term efficacy of Pertzye was evaluated in a randomized, double-blind, placebo-controlled, crossover study of 24 patients with EPI caused by cystic fibrosis. Subjects received an individually titrated dose of Pertzye (≤2,500 lipase units/kg/meal) or matching placebo for 6 to 8 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 8 days. The mean coefficient of fat absorption was 83% with Pertzye compared to 46% with placebo (difference of 36%, 95% CI, 28%–45%; 

<.001). The mean change in coefficient of nitrogen absorption also favored Pertzye, compared to placebo (difference of 32%; 

 The dosage of Pertzye should be individualized based on clinical symptoms, the degree of steatorrhea present, and fat content of the patient's diet. It should be initiated at the lowest recommended dose and gradually increased. Specific dosing guidance has been published by the Cystic Fibrosis Foundation. In general, for children >12 months and younger than 4 years of age and weighing ≥8 kg, dosing should begin at 1,000 lipase units/kg of body weight/meal to a maximum of 2,500 lipase units/kg/meal, ≤10,000 lipase units/kg/day, and <4,000 lipase units/g fat ingested/day. Adults and children ≥4 years of age and weighing ≥16 kg should begin with 500 lipase units/kg/meal with similar limits. Half of the prescribed dose given for an individual full meal should be taken with each snack. Attempting to divide the capsule contents in small fractions to deliver small doses of lipase is not recommended. 

FDA has approved pancrelipase delayed-release capsules to treat exocrine pancreatic insufficiency resulting from cystic fibrosis or other conditions.

Pancrelipase DR caps approved for EPI

The most common adverse reactions (≥2%) observed in subjects during the three placebo-controlled clinical trials of avanafil included headache, flushing, nasal congestion, nasopharyngitis, and back pain. Patients receiving avanafil for an additional 40 weeks during a long-term safety study did not experience worsening of adverse effects over time. The use of avanafil along with antihypertensive agents, particularly alpha-blockers, or substantial amounts of alcohol (>3 units) may lead to hypotension. Like all PDE5 inhibitors, patient taking avanafil may rarely develop a sudden decrease or loss of hearing, accompanied by tinnitus or dizziness, or non-arteritic anterior ischemic optic neuropathy.  

. The recommended dose of avanafil for most patients is 100 mg taken with or without food approximately 30 minutes before sexual activity on an as-needed basis, but no more than once daily. The dose of avanafil may be increased to 200 mg or decreased to 50 mg based on efficacy and/or tolerability, with the preferred dose being the lowest providing benefit. No dosage adjustment in mild-to-moderate renal dysfunction is required. Avanafil should not be used in patients taking a nitrate or a strong CYP3A4 inhibitor, and no more than 50 mg in a 24-hour period should be used in patients concomitantly taking a moderate CYP3A4 inhibitor or a stable dose of an alpha-blocker. Avanafil should not be used when sexual activity is inadvisable because of cardiovascular or other reasons.  

Open-angle glaucoma is the most common type of glaucoma, accounting for at least 90% of all cases, and affecting about 3 million Americans. On February 10, FDA approved tafluprost (Zioptan, Merck) ophthalmic solution 0.0015% to reduce elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Tafluprost (acid) is a prostaglandin analog, which is believed to reduce IOP by increasing uveoscleral outflow of aqueous humor.  

Tafluprost ophthalmic solution 0.0015% was evaluated in five controlled clinical studies of up to 24 months duration. In study subjects with open-angle glaucoma or ocular hypertension, baseline pressures of 23 to 26 mmHg, and treated with tafluprost dosed once daily in the evening, reductions in IOP at 3 and 6 months of 6 mmHg to 8 mmHg and 5 mmHg to 8 mmHg, respectively, were observed.   

 The safety of tafluprost ophthalmic solution 0.0015% was evaluated in 905 patients during the five controlled clinical studies. The most common adverse reaction observed in patients treated with tafluprost was conjunctival hyperemia, which was reported in between 4% and 20% of study subjects. Other ocular adverse reactions reported in at least 2% of subjects during clinical trials included: ocular stinging/irritation (7%), ocular pruritus including allergic conjunctivitis (5%), cataracts (3%), dry eye (3%), ocular pain (3%), eyelash darkening (2%), growth of eyelashes (2%), and blurry vision (2%). Of note, brown pigmentation of the iris and periorbital tissue (eyelid) can also occur and may be permanent, but is not typically noticeable for months to years after drug initiation. 

 The recommended dose is 1 drop of tafluprost ophthalmic solution 0.0015% in the conjunctival sac of the affected eye(s) once daily each evening. The dose of tafluprost should not exceed once daily since it has been shown that more frequent administration of prostaglandin analogs may lessen the IOP-lowering effect. Tafluprost ophthalmic may be used concomitantly with other topical ophthalmic drugs to lower IOP; however, each one should be administered at least 5 minutes apart.   

FDA approves oral inhibitor for ED

In SELECT, the most common adverse effects of lucinactant are related to its administration down a premature infant's endotracheal tube and include endotracheal tube reflux (18 events per 100 doses), skin paleness (9 events per 100 doses), and endotracheal tube obstruction (6 events per 100 doses), often resulting in infants' needing a dose interruption (9 events per 100 doses). Administration-related adverse reactions were more common in premature infants receiving lucinactant compared to control surfactants. Oxygen desaturation was reported in 17%, 9%, and 13%, and bradycardia for 5%, 2%, and 3% of infants treated with lucinactant, colfosceril palmitate, and beractant, respectively. 

 The recommended dose of lucinactant is 5.8 mL/kg birthweight administered by intratracheal administration. Up to 4 doses of lucinactant can be administered in the first 48 hours of life; however, doses should be given no more frequently than every 6 hours. Dosing should be interrupted if administration-related adverse reactions occur.  

FDA approves Lucinactant and Peginesatide