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?>