New Treatment for Community Acquired Pneumonia

Cempra's solithromycin has recently received fast-track status from the FDA. Solithromycin is a next-generation macrolide, a fluoroketolide, which has strong activity against macrolide-resistant bacterial strains.

A New Drug Application is expected in 2016 for the treatment of community-acquired bacterial pneumonia. Solithromycin, otherwise known as CEM-101, is under phase 3 trials for this indication. Under the GAIN (Generating Antibiotic Incentives Now)  law, solithromycin was granted status as a Qualified Infectious Disease product. Both IV solution and oral capsules obtained this status for the treatment of community acquired pneumonia, while the capsules obtained QIDP status for the treatment of gonorrhea.

Aside from its phase 3 trials for CABP, solithromycin is also undergoing a phase 3 trial for uncomplicated gonorrhea, phase 2 for COPD and nonalcoholic steatohepatitis, and phase 1 trial in pediatric populations. Thus far, studies have shown solithromycin to be a well-tolerated and safe treatment.

Source:
http://www.pharmacytimes.com/product-news/bacterial-pneumonia-treatment-fast-tracked-by-fda

New App for Movie Buffs with Overactive Bladder

Technology to the rescue once again! Astellas Pharma U.S. has sponsored a new app called "RunPee" for moviegoers with overactive bladder. This app features a timer that the user starts at the beginning of the movie. From there, the phone will vibrate and the user will be alerted of one to four key moments in the movie where they can get up to use the restroom without missing critical plot points or laugh-out-loud moments. The alerts include text of the lines from the movie that will serve as the cue to leave, as well as how long the use has to use the restroom before missing a key moment, and how long it will be until the next bathroom-break opportunity. In addition, there is a synopsis of the first few minutes of the movie, as well as informing the user of whether or not there is anything featured after the credits. While the app title may seem like a bit of tongue-in-cheek humor, this condition is a serious problem that can be embarrassing and have devastating impacts on quality of  life... This app can very well be a game changer for movie-loving sufferers of OAB.

The Importance of Counseling

The Pharmacy Times recently posted an article concerning a $500,000 settlement with Walgreens regarding noncompliance with counseling laws in California. According to the lawsuit, pharmacists were not routinely counseling on new prescriptions or dose changes as mandated by law. Counseling is undoubtedly one of the most important aspects of a pharmacist's career. It is our chance to use our clinical knowledge to educate our patients and make sure they fully understand how to appropriately take there medications. Counseling is where we can warn our patients about potentially dangerous adverse events of their medications so they can catch problems early on in their treatment. It also gives us another chance to look at the patient's prescription and catch any mistakes that may have inadvertently slipped through the verification process. It seems like common sense to mandate counseling on all new prescriptions. However, this is not the case. Many states only require an offer to counsel. In a world where we are all on-the-go and expect our prescriptions to be processed at the same speed with which we get our Big Macs, many people will simply turn down the offer for pharmacist counseling. "I've got places to be!" The sense of urgency is just as problematic on the pharmacy side of the equation. With the time crunches and quotas hanging over many pharmacists' heads, the sense of pressure can be indescribable. Especially in large, high-volume stores, breaking the workflow and taking time to counsel on every new prescription can seem like an inconvenience. After all, the patients often get handouts describing how to take their medications; they can just read over those at home, right? For those few monographs that escape their untimely fates in the trash cans just outside the doors of the pharmacy, let us consider the fact that the average adult in the United States has a 9th grade reading level (2). Health literacy is an enormous issue in our country, and we cannot rely on patient comprehension of monographs for proper drug education. As pharmacists, we need to ensure that we take those extra few minutes to thoroughly counsel our patients, and assess their understanding of how to use their medications. This is what we have undergone all of those rigorous years of schooling to do. You never know when your intervention will be the difference between high-quality healthcare and a fatal medication error.




Sources:
1. http://www.pharmacytimes.com/news/walgreens-settles-pharmacist-consultations-lawsuit
2. http://www.impact-information.com/impactinfo/literacy.htm

The Little Pink Pill Approved

On Tuesday August 18th the FDA finally approved the highly controversial Addyi (flibanserin), more commonly referred to as "the little pink pill," after two previous denials. The medication, being touted as the female Viagra, is indicated for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. HSDD is defined as "low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of another drug substance."

While Addyi is a 5HT 1A agonist and 5HT 2A antagonist, its exact mechanism in relieving the effects of HSDD is unknown. The most common side effects of this medication are dizziness, fatigue/somnolence, nausea, insomnia and dry mouth. It should be dosed at bedtime to reduce the risks of falls or adverse events from CNS depression, hypotension and syncope. Addyi is certainly not without risk; the approval comes with a Black Box Warning for a risk of severe hypotension and syncope when used in combination with alcohol, strong CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, itraconazole, diltiazem, grapefruit juice, etc), or impaired liver function.

Trials for the approval of this medication included three 24-week randomized, double-blind, placebo control trials with an average participant age of 36 years. Women reported the number of "satisfying sexual events," sexual desire (scale of 1.2 to 6), and distress related to low sexual desire (scale of 0 to 4). The number of satisfying sexual events increased from 0.5 to 1 additional event compared to placebo  per month. The sexual desire score increased by 0.3 to 0.4, and the distress score related to sexual desire decreased by 0.3 to 0.4 over placebo. Patients may have difficulties obtaining access to Addyi, as it can only be dispensed by REMS-certified physicians and pharmacies. It is yet to be determined if the modest benefits will outweigh the obvious risks of this medication.

SOURCE:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm458734.htm

Staying Safe in the Summer Heat

The Pharmacy Times recently posted an article summarizing the results of a trial that looked at folic acid supplementation and blood flow to the skin. As described in the article, when we are exposed to heat, the combination of sweating and increased blood flow to the skin is our body's way of cooling itself down. However, elderly patients typically have decreased perfusion in the skin and this thermoregulatory mechanism becomes less effective. This also puts these individuals at greater risk for cardiovascular events and heat stroke.

The study discussed in the article looked at chronic folic acid supplementation of 5 mg per day for 6 weeks, as well as direct administration of folic acid to the skin via intradermal microdialysis fibers. The theory behind this was that folic acid can increase the bioavailability of BH4, which stimulates nitric oxide production, an essential mechanism of blood vessel dilation and increasing blood flow in the skin. The researchers performed both localized heating studies and whole-body heating studies. For localized studies, patients were their own controls, as either folic acid or placebo were administered at randomized sites on their arms via the microdialysis fibers.  In whole-body heating studies, the patients' skin temperatures were controlled using water-perfused wetsuits. The trials found there was increased nitric oxide production at the locations treated with folic acid, increased cutaneous vascular conductance, and nitric-oxide dependent vasodilation.

The results of this study suggest that folic acid can improve blood vessel health. The researchers stated that they would like to further investigate if this mechanism is as effective in elderly patients with established cardiovascular disease. They suggest that talking to patients about folic acid supplementation, or adding in a daily multivitamin, may be an important counseling point to keep in mind during the warm summer months.

sources:
1. http://www.empr.com/news/folic-acid-may-help-elderly-handle-heat-waves/article/406858/
2. http://www.pharmacytimes.com/resource-centers/vitamins-supplements/weather-heat-waves-with-folic-acid-supplements

Smart Contact Lens an Eye-Opener for Diabetics

I previously wrote a blog post about Novartis teaming up in creating the world's first robotic pill. Novartis is at it again, this time partnering with Google, to create what they are calling a "smart contact lens." Google recently received a patent for this product. The lens will house a small microchip that, via a small pinhole, will analyze the glucose concentration in the tears to measure the wearer's blood glucose levels. Once again, this new implementation of technology could open doors for the advancement of modern medicine. As discussed in the article, the need to prick your fingers limits how often you can test your blood sugar throughout the day. In addition, fingersticks can significantly impede compliance for a large number of patients with needle phobias. The contact lens circumvents both of these issues by reducing the need for fingersticks and allowing more frequent blood sugar readings and in theory, better overall glucose control and decreased morbidity and mortality because of it. Novartis is leading the way in modern medicine, and I am eager to observe the implementation and reception of these products when they hit the market!

Source:
http://time.com/3758763/google-smart-contact-lens/

Loperamide & Omeprazole: Potential for Abuse?

As pharmacists, it is important to stay aware of potential drugs of abuse. In the Colleagues Interact section of Pharmacists Letter, there was a conversation feed about surprising drugs of abuse. One pharmacist stated that they had seen omeprazole and loperamide being used together inappropriately. The science behind it does appear to make sense... Loperamide is a peripherally acting mu-receptor agonist. Not only does omeprazole inhibit CYP3A4, one of the enzymes responsible for metabolizing loperamide, but also inhibits p-glycoprotein which plays a large role in keeping drugs from crossing the blood brain barrier. This combination means loperamide would not only be at higher concentrations in the body, but also have greater potential to cross the blood brain barrier and affect the central nervous system. However, a 2010 review by Vandenbossche et al noted that of 10 studies performed, only one trial supported that inhibition of p-gp could lead to the development of clinically relevant central nervous system effects. It does not appear as though omeprazole has any sort of substantial contribution to the effects that people observe when abusing loperamide.

Vaults of Erowid, a member-supported website that includes information about drugs of abuse does show that loperamide is quite frequently abused. This was a reference frequently utilized in the substance abuse class at the University of Iowa College of Pharmacy. A normal dose of loperamide is 8 mg or less per day. Individuals on this site report using upwards of 30mg, and frequently use it as a way of controlling opiate withdrawal symptoms and inducing a "mild euphoria." It goes without saying that doses of loperamide this high can have disastrous effects on gastrointestinal health, risking severe constipation, intestinal obstruction, if not complete ileus. While making a substance abuse intervention of this nature would be difficult, it is important to be cognizant of what these drugs may be being used for when individuals buy them in combination.



1.Vandenbossche J, Huisman M, Xu Y, Sanderson-Bongiovanni D, Soons P. Loperamide and P-glycoprotein inhibition: assessment of the clinical relevance. J Pharm Pharmacol. 2010;62:(4)401-12. [pubmed]

Robotic Pills?

Rani Therapeutics, a US start-up company, and Novartis are teaming up to create the first "robotic pill" which will be the first oral agent to deliver biologic drugs. The study will determine which biologic drugs are compatible for administration via Rani's robotic technology. A large focus of the study will look at the technology's ability to administer insulin to diabetic patietns.

So how does it work? Acid in the digestive system corrodes the pill's external coating, exposing an internal valve that separates citric acid and sodium bicarbonate. As the valve becomes exposed, the bicarb and citric acid mix and to form carbon dioxide. As the CO2 is produced, it inflates a balloon-like structure that is covered in microneedles made of sugar that contain the drug. As the balloon inflates, the needles make subcutaneous injections into the intestinal wall. The balloon then detaches and slowly dissolves as it moves through the GI tract.

This new technology is part of the recent trend in merging technology and medicine. If approved, this could open doors for new medical advancements that vastly improve the quality of our patients' lives and extend overall life expectancy.

References:
http://www.pharmacytimes.com/publications/issue/2015/july2015/robotic-pills-could-simplify-administration-of-biologic-drugs

Lamotrigine Interaction with Contraceptives

There is a well-known bi-directional interaction between lamotrigine and contraceptives. Contraceptives, when coadministered with lamotrigine, can decrease lamotrigine levels by up to 50%. For patients who are using this to control a seizure disorder, this puts them at a substantially increased risk of seizures. Lamotrigine can also decrease the efficacy of progestins. For women who are on the progestin-only contraceptives such as the mini-pill or Mirena IUD, they are at a risk of contraceptive failure. It has not been fully established whether or not there is a risk of contraceptive failure on combination hormonal products, so patients are advised to use other methods of contraceptives (diaphragm, condoms) while taking lamotrigine.

For patients who were on lamotrigine prior to initiating birth control, they will require an increase in dose. For patients who were already on birth control prior to starting the lamotrigine, this interaction is less of a safety concern. In this scenario, doctors will have to gradually taper up to the effective dose for the patient. It is important to note that patients on birth control may require higher-than-normal doses of lamotrigine. Also, doctors must be aware that they will likely have to decrease the dose of lamotrigine if the patient decides to stop using their birth control.

1 Lexicomp Drug Interactions>
2 .Micromedex Drug Interactions
3. Facts & Comparisons Drug Interactions
4. Oral Contraceptives Reduce Lamotrigine (Lamictal) Blood Levels <link>

3D Printed Drugs

A recent article in the Pharmacy Times (link to article) highlighted the FDA approval of Spritam (levetiracetam), the first 3D-printed drug. As discussed in the article, the 3D printing technology bonds thin layers of the powdered medication via an aqueous fluid. This technology allows the pill to rapidly dissolve with just a small sip of liquid, which is highly beneficial for epileptic patients who may have difficulties swallowing. The most common side effects in adults were sleepiness, weakness, dizziness, and infection. Children who used Spritam experienced aggressive behavior, irritability, fatigue, congestion, and loss of appetite.

This article begs the question: is 3D printing technology going to become the future of medicine? Will we ever reach a day where it becomes standard for patients to have 3D printing technology and can "print" their medications from home? It will be interesting to see where the future of pharmaceutical 3D printing takes us.

Vitamin D Interactions & IU Dosing Conversions

Today I was asked to analyze the clinical relevance of a drug interaction (severe rating, Lexicomp) between sucralfate and vitamin D3 with specific regards to patients with CKD. The concern was that vitamin D enhances the absorption of the aluminum from sucralfate, which is already a concern in renal failure patients. However, the trials referenced in the interaction report listed the vitamin D dosages in micrograms rather than IU, which is how it is typically dispensed in the community setting. To determine the relevance of this, I had to convert this dose back to IU. We don't have heavy coverage on nutrition in pharmacy school, but I found the following list of conversions to calculate dose in mcg from international units that I thought others may need or find useful.

• To convert Vitamin A as retinol: 
      From IU to mcg:  IU * 0.3 = mcg
      For example: 5000 IU * 0.3 = 1500 mcg
      From mcg to IU: mcg / 0.3 = IU 

• To convert Vitamin A as beta-carotene: 
      From IU to mcg:  IU * 0.6 = mcg
      For example: 5000 IU * 0.6 = 3000 mcg
      From mcg to IU: mcg / 0.6 = IU 

• To convert Vitamin D: 
      From IU to mcg: IU * 0.025 = mcg 
      For example: 400 IU * 0.025 = 10 mcg
      From mcg to IU: mcg / 0.025 =IU 

• To convert Vitamin E if the product label has DL-Alpha-tocopherol as the ingredient:
      From IU to mg: IU * 0.9 = mg 
      For example:  30 IU * 0.9 = 27 mg 
      From mg to IU: mg / 0.9 = IU

• To convert Vitamin E if the product label has D-Alpha-tocopherol as the ingredient:
      From IU to mg: IU * 0.67 = mg. 
      For example: 30 IU * 0.67 = 20.1 mg
      From mg to IU: mg / 0.67 = IU
For those not keen on math, here is a link to an automatic calculator:

http://www.robert-forbes.com/vitamin-converter

Returning to the topic of the drug interaction, the trial referenced in Lexicomp (Fournier et al, available here from PubMed: D3 & sucralfate) administered 6 micrograms per week (240 IU) to patients on hemodialysis and found this to significantly increase the patients' plasma aluminum concentrations. This increased concentration was maintained for up to 6 weeks after D3 was discontinued. Therefore, it can be inferred that this would be a clinically relevant interaction for a majority of patients. 

Presentation of Aluminum Toxicity

• Osteomalacia
• Premature osteoporosis  
• Mental status changes
• Proximal muscle weakness
• Bone pain
• Nonhealing fractures
• Anemia

References:

1. Yuan B, Klein MH, Contiguglia RS, et al. The role of aluminum in the pathogenesis of anemia in an outpatient hemodialysis population. Ren Fail. 1989;11:(2-3)91-6. [pubmed]

2. "Aluminum Toxicity." : Background, Pathophysiology, Epidemiology. Web. 7 Aug. 2015. <http://emedicine.medscape.com/article/165315-clinical)>.

3. Fournier A, Demontis R, Tahiri Y, et al. 1 alpha OH vitamin D3 increases plasma aluminium in haemodialysed patients taking Al (OH)3. Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1985;21:390-4. [pubmed]

OTC Heartburn Counseling: Alarm Symptoms and What They Might Mean

Symptoms Requiring MD Referral During OTC Counseling for Heartburn 3

·         Heartburn >3 months      ·         Heartburn persisting after 2 weeks of OTC treatment      ·         Heartburn persisting  while on appropriate dose of Rx or OTC PPI/H2RA      ·         Nocturnal  heartburn      ·         Dysphagia/difficulty swallowing      ·         Vomiting blood/black tarry stools      ·         Chronic hoarseness/wheezing/cough      ·         Unintentional weight loss      ·         Persistent nausea/vomiting/diarrhea      ·         Chest pain accompanied by MI symptoms      ·         Children <2 (antacid), children <12 (H2RA), <18 (PPI)      ·         < 45 years old with new-onset heartburn

GERD Presentation 1 (occurring > 2x/week, or interfering with ADL’s)	Peptic Ulcer Disease Presentation4
·         Heartburn, burning sensation may spread to throat  accompanied by sour taste      ·         Chest pain      ·         Dysphagia      ·         Dry cough      ·         Hoarseness      ·         Sore throat      ·         Regurgitation      ·         Lump-in-throat sensation	·         Heartburn      ·         Localized pain/discomfort in center of abdomen      ·         Symptoms improved when patient has empty stomach or eats to satiety      ·         Blood in vomit, stools      ·         Fatigue, dyspnea (signs of anemia)      ·         Dyspepsia- belching, bloating, distention

GERD Risk Factors1	PUD Risk Factors5
·         Obesity      ·         Hiatal hernia           ·         Pregnancy      ·         Smoking      ·         Dry mouth      ·         Asthma      ·         Diabetes      ·         Delayed stomach emptying      ·         Connective tissue disorders (scleroderma)	·         Smoking      ·         Heavy alcohol use      ·         Elderly      ·         Family history      ·         ICU patients      ·         Illicit drug use o   Crack cocaine, methamphetamine      ·         Regular NSAID use

References:

1. "GERD." Causes. Web.29 July 2015. <http://www.mayoclinic.org/diseases-conditions/gerd/basics/symptoms/con-20025201>.

2. Katz, Philip O, Lauren B Gerson, and Marcelo F Vela. "Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease." Am J Gastroenterol The American Journal of Gastroenterology (2013): 308-28.

3. Facts & Comparisons. Accessed 3 August 2015. <www.online.factsandcomparisons.com.proxy.lib.uiowa.edu>

4. "Peptic Ulcer Disease Clinical Presentation." Peptic Ulcer Disease Clinical Presentation: History, Physical Examination, Staging. Web. 4 Aug. 2015. <http://emedicine.medscape.com/article/181753-clinical>.

5. "Peptic Ulcer Disease." Causes, Diagnosis & Treatments. Web. 4 Aug. 2015. <https://www.clinicalkey.com/topics/gastroenterology/peptic-ulcer-disease.html>.

6. Vakil, NB. Peptic ulcer disease: Management. In: UptoDate. Feldman M (Ed). UpToDate. Accessed 8/4/15. < http://www-uptodate-com.proxy.lib.uiowa.edu/contents/peptic-ulcer-disease-management?source=machineLearning&search=peptic+ulcer+disease&selectedTitle=1~150&sectionRank=1&anchor=H19#H17>

7. Crowe, SE. Treatment regimens for Heliobacter pylori. In: UpToDate. Feldman, M (Ed). UpToDate. Accessed 8/4/15. < http://www-uptodate-com.proxy.lib.uiowa.edu/contents/treatment-regimens-for-helicobacter-pylori?source=see_link> 

New Emergency Contraceptive Option

Ella (ulipristal) is a relatively new emergency contraceptive option for women. Previous emergency contraceptives, like Plan-B, were only effective of up to 72 hours unlike Ella which remains effective for up to five days. One potential drawback is that Ella requires a prescription, which may deter some women, especially teens, from seeking out its use.

Dose: 30 mg; take as soon as possible up to 5 days after intercourse or suspected contraceptive failure

Contraindications: Known or suspected pregnancy

Adverse effects:

• Headache (18%)
• Abdominal pain (12%)
• Nausea (12%)
• Dysmenorrhea (9%)
• Fatigue (6%)
• Dizziness (5%)

Precautions:

• Continue or start patient's regular contraception after using Ella
• Do not repeatedly use Ella in a single menstrual cycle
• If next period is delayed by more than one week, evaluate patient for pregnancy
• Patients who become pregnant or experience lower abdominal pain require evaluation for ectopic pregnancy

Resources:

1. http://www.ellanow.com

2. Lexicomp. Ella. Accessed 8/5/2015. Available at: <http://online.lexi.com.proxy.lib.uiowa.edu/lco/action/doc/retrieve/docid/patch_f/2856384#coi>

Important Patient Counseling Points for Procrit

USED FOR:

Treatment of anemia by stimulating the growth of red blood cells

PRIOR TO ADMINISTRATION:

• Keep refrigerated (DO NOT FREEZE) and protected from light
• Do NOT shake the vial
• Check the expiration date, and make sure the solution is clear and colorless with no particulate matter inside
• Prepare supplies for injection, wash hands well

ADMINISTRATION:

Can be injected subcutaneously or IV (hemodialysis patients)

1.       Do not inject into an area that is tender/bruised/hard/has scars or stretch marks

a.       Acceptable injection sites:

                                                                           i.      Outer portion of upper arm

                                                                         ii.      Abdomen

                                                                        iii.      Front middle thigh

                                                                       iv.      Upper outer area of buttocks

2.       Clean area with an alcohol wipe, let dry

3.       Use free hand to pinch a fold of the skin at the desired injection site, keeping hands away from the cleaned area

4.       Use a quick motion to insert at 90 degree or 45 degree angle and inject the prescribed dose.

5.       Remove syringe and hold gauze or cotton ball over injection site for several seconds

6.       Dispose of the syringe & needle in an appropriate container

BLACK BOX WARNING 

Increased risk of death, MI, stroke, VTE, tumor progression

o   At risk patients: CKD, patients with breast, NSCLC, head and neck, lymphoid and cervical cancers, perisurgery patients (require VTE prophylaxis)
        

SIDE EFFECTS

• Injection site irritation, increased BP, fever, headache, upset stomach, joint pain, and cough
• Let doctor know if you experience racing heart, chest pain, severe dizziness
• Increased risk of clotting: monitor for redness, swelling, warmth, pain in extremities

Resources:
1. Procrit Instructions for use. <http://assets.procrit.com/shared/product/procrit/procrit-instructions-for-use.pdf>
2. Lexicomp. Available at <http://online.lexi.com.proxy.lib.uiowa.edu/lco/action/home/switch>
3. Facts & Comparisons. Available at <http://online.factsandcomparisons.com.proxy. lib.uiowa.edu/index.aspx?>