A Benefit Risk Review of Pediatric Use of Hydrocodone/Chlorpheniramine, a Prescription Opioid Antitussive Agent for the Treatment of Cough.

Hydrocodone/chlorpheniramine is a prescription opioid licensed in the USA for the relief of cough and upper respiratory symptoms associated with allergy or cold in adults, previously contraindicated in children aged < 6 years. We present findings from a modern benefit risk review of hydrocodone/chlorpheniramine use as an antitussive agent in patients aged 6 to < 18 years. A cumulative search of the manufacturer's pharmacovigilance database covering 1 January 1900-7 August 2017 identified all individual case safety reports (ICSRs) associated with product family name "hydrocodone/chlorpheniramine." The search was inclusive of all MedDRA system organ classes, stratified by age (< 18 years). A comprehensive review of the scientific literature was conducted on safety and efficacy of opioids for pediatric treatment of cough. Three hundred and ninety-one ICSRs associated with hydrocodone/chlorpheniramine were identified; 35/391 ICSRs were in patients < 18 years of age; 18 were considered serious. Four fatalities were reported in patients 6 to < 18 years; two fatalities involved co-suspect medication azithromycin and two were poorly documented. Our literature search identified no robust efficacy data for hydrocodone/chlorpheniramine in the relief of cough and upper respiratory symptoms associated with allergy or cold in patients aged 6 to < 18 years. As we found no evidence of hydrocodone/chlorpheniramine efficacy in the pediatric population, we conclude that the benefit risk profile is unfavorable. This evidence contributed to the US Food and Drug Administration's (FDA's) recent decision that hydrocodone-containing cough and cold medications should no longer be indicated for treatment of cough in patients < 18 years, highlighting the value of proactive re-evaluation of the benefit risk profile of older established drugs. Plain Language Summary People often use medicines containing opioids to treat cough symptoms. The US Food and Drug Administration (FDA) recently decided that cough medicines containing opioids should not be used by children under 18 years old. Part of this decision was a review of the benefits and risks of using cough medicines that contain the opioid hydrocodone in children.Why was this review carried out? Most cough medicines that doctors can prescribe were approved several decades ago. Since then, rules for the approval of medicines have become stricter. In this review, researchers looked at the safety of hydrocodone, and how well this opioid relieves cough symptoms in children. Up-to-date information and modern research methods were used.The two key pieces of evidence found were: We could not locate any clinical trials providing robust evidence for the use of hydrocodone for cough relief in children under 18 years of age. (Outside the scope of this review, a number of clinical trials of hydrocodone-containing cough medicines in adults aged 18 years and over have shown the medicine to be effective in these patients.) Cough medicines containing opioids can cause harmful side effects in children such as breathing problems. In the research reported here, ten children died after taking a hydrocodone-containing cough medicine. Nine of these deaths were due to overdose. This evidence was used to draw the following conclusions: In children under 18 years of age, the risks of using hydrocodone for cough relief are greater than any benefits. Older medicines should be reviewed regularly to look at their safety and how well they are working using up-to-date evidence.

Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery.

The overall study goal was to produce a microparticle formulation containing atropine sulfate for ocular administration with improved efficacy and lower side effects, compared with that of the standard marketed atropine solution. The objective was to prepare an atropine sulfate-loaded bovine serum albumin-chitosan microparticle that would have longer contact time on the eyes as well as better mydriatic and cycloplegic effect using a rabbit model. The microparticle formulation was prepared by method of spray-drying technique. The percent drug loading and encapsulation efficiency were assessed using a USP (I) dissolution apparatus. The particle sizes and zeta potential were determined using laser scattering technique and the surface morphology of the microparticles was determined using a scanning electron microscope. The product yield was calculated from relative amount of material used. In vitro cytotoxicity and uptake by human corneal epithelial cells were examined using AlamarBlue and confocal microscopy. The effects of the microparticle formulation on mydriasis in comparison with the marketed atropine sulfate solution were evaluated in rabbit eyes. The prepared microparticle formulation had ideal physicochemical characteristics for delivery into the eyes. The in vivo studies showed that the microparticles had superior effects on mydriasis in rabbits than the marketed solutions

Spray-dried doxorubicin-albumin microparticulate systems for treatment of multidrug resistant melanomas.

As multidrug resistance continues to be a problem in cancer treatment, controlled release delivery systems, such as microspheres, may aid to give a slower release of anticancer drugs into drug resistant tumor cells. In this study doxorubicin microspheres microencapsulated in an albumin matrix were prepared via the spray-drying method and characterized for particle size, content analysis, and release studies. They were then evaluated in vitro using drug resistant murine melanoma tumor cells for uptake and efflux studies. Spray-drying produced a dispersed powder with a mean particle size of 4.91 ± 1.2 µm, 60% product yield, and encapsulation efficiency of 85% and a ζ potential range of 37 to -40 mV. Intracellular doxorubicin concentrations were higher in drug resistant tumor cells treated with microspheres as opposed to solution, and efflux of doxorubicin from the tumor cell was inhibited. Greater cytotoxic effects were seen in tumor cells treated with doxorubicin microspheres versus solution up to and after 3 days. In vivo pharmacokinetic studies conducted in male Sprague-Dawley rats, revealed a plasma-level time curve indicative of a two-compartment model, and showed prolonged half-life of doxorubicin, greater area under the plasma concentration time curve, and increased plasma concentrations of doxorubicin in rats at 8 and 24 h after administration of doxorubicin microspheres.