Featured

About this Blog:

As a pharmacist, I am used to providing medical information to patients, and like many health care professionals I am disturbed by the amount of misinformation available on the internet. My goal in writing this blog is to provide quality information on pharmacy and health care issues by researching them and creating short, factual posts that give an introduction to a topic, and when available, to include links to additional information for those who are interested in learning more. My choice of topics will typically be things that have been central to my career and training including pharmaceuticals, public health, and diabetes. Any comments or suggestions are always welcome.

Follow me on Twitter @hhommel

New COVID treatments

Recently the FDA granted emergency use authorization for two oral antiviral medications to treat COVID-19. This is a huge step forward in the fight against the virus since these medications can be taken at home. This will help ease the strain on hospitals, many of which are overcrowded with COVID patients as we enter the second winter of the pandemic.

The first authorization was for a drug called Paxlovid, made by Pfizer. Paxlovid is a combination of two antivirals; nirmatrelvir and ritonavir. Nirmatrelvir inhibits a protease called Mpro, preventing viral replication. Ritonavir is taken with nirmatrelvir to slow its metabolism, making it more effective. The two medications must be taken together in order to be effective. Paxlovid is taken for 5 days, and should be started within 5 days of symptom onset. It is authorized for emergency use in patients 12 years of age or older, who have tested positive for COVID and are at high risk of developing severe COVID.

The second authorization was for a Merck drug called molnupiravir (Lagevrio). It can be used in patients 18 years and older who have tested positive for COVID and are at high risk of progression to severe COVID. Molnupiravir works by forming a compound called NHC which disrupts the viral genome and stops it from multiplying. Molnupiravir is also taken for 5 days, and should be started within 5 days of symptom onset. Recent studies have shown molnupiravir to be less effective than the initial clinical trials, but the drug may have different levels of efficacy for different viral variants. More info here Merck’s COVID pill loses its lustre: what that means for the pandemic (nature.com)

Remdesivir is another antiviral also in use for COVID treatment, but it is given as an intravenous infusion in the hospital.

Other medications currently being studied for treatment of COVID include nitazoxanide, interferons, stem cells, colchicine, fluvoxamine, ivermectin, and corticosteroids.

For more information see COVID-19 Treatment Guidelines (nih.gov)

PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) For Patients (covid19oralrx-patient.com)

Molnupiravir dosing, indications, interactions, adverse effects, and more (medscape.com)

Once-weekly Insulin?

Many diabetes patients have to take multiple daily injections of insulin, so the potential for reduced frequency of dosing provided by an ultra-long-acting insulin sounds like a very convenient innovation.

Insulin icodec, a Novo Nordisk product, is currently in development and has a half life of about 196 hours which would allow for once-weekly dosing. Icodec is an insulin analog (a modified insulin), with 3 substituted amino acids. These substitutions provide stability and protect against degradation by enzymes in the body. The addition of a long chain fatty acid to the molecule allows it to bind to albumin, a protein in the blood. Binding to albumin creates an insulin depot that steadily releases over the course of about 7 days, providing sustained insulin levels from a single injection.

A 26-week study of 247 patients compared safety and efficacy of icodec to insulin glargine (Lantus, Basaglar). Results showed similar glucose-lowering effects and comparable safety profiles.

For many patients, including those with Type 1 diabetes, mealtime (short acting) insulin injections will still be necessary, but the convenience of once weekly basal insulin dosing may be appealing.

My concern with an insulin that has such a prolonged duration of action is one of safety. Dosing errors with a medication like this may require a hospital stay to monitor blood sugar levels and prevent potentially fatal hypoglycemia. The potential for reduced food intake due to illness, that occurs several days after an injection could also lead to dangerously low blood sugar levels.

Further studies will need to address safety issues that can occur outside of clinical trials. Ultimately this medication may prove to be a good alternative for carefully selected patients.

For more info:

238-OR: Once-Weekly Basal Insulin Icodec Offers Comparable Efficacy and Safety vs. Once-Daily Insulin Glargine U100 in Insulin-Naïve Patients with T2D Inadequately Controlled on OADS | Diabetes (diabetesjournals.org)

Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment | NEJM

COVID-19 Coronavirus Facts

The spread of the new coronavirus has created a lot of confusion, misinformation, and panic. The situation changes daily and our understanding of the disease is rapidly evolving.

Here are some things we now know about the COVID-19 coronavirus:

On average, about 5 new countries each day are reporting COVID-19 cases for the first time. The hardest hit countries so far are China, Italy, Iran and South Korea.

Worldwide cases have exceeded 100,000 and deaths worldwide are now over 3000. This suggests a mortality rate of about 3%, but that estimate is likely too high and should come down as more mild cases are identified. Sicker patients will seek care, while patients with mild symptoms may go undetected, leading to inflated mortality rates.

Even a 1% mortality rate may seem relatively safe but would place an enormous burden on hospitals, morgues and other medical services, and would be devastating to the economy. For example, in a city with a population of one million, assuming only 5% get the disease, that means 50,000 would be sick. Most (about 80%) would be mild cases, but 20% may require hospitalization. That’s 10,000 people in the hospital, and 500 deaths, possibly over a short period of time, like a few weeks. However, these calculations assume the disease spreads unchecked, which will not happen.

So far the disease appears to be most dangerous to older patients and those with chronic illnesses. Severe symptoms in children appear to be uncommon. A study in China, where the most cases are, showed that women and children were less likely to die from the virus than men. More about that here https://www.bbc.com/news/health-51774777

Public health efforts will focus on identifying cases, learning how it spreads, stopping the spread, and developing vaccines and treatments. Tests are available now, vaccines may be months away, and antivirals are being tested to see if they can help alleviate symptoms.

In the United States, there are still 2 states that have not yet started testing patients for coronavirus- Maine, and West Virginia. Some other states have only started testing in the last few days. This will likely lead to a spike in reported cases where the virus has already been spreading for days or weeks.

The best thing to do at this point is wash your hands frequently, try not to touch your face, stay at home if you are ill, seek medical care if you have flu-like symptoms (cough, fever), and stay informed.

Daily updates are available:

from the World Health Organization at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

or from the Center for Health Security at Johns Hopkins http://www.centerforhealthsecurity.org/resources/COVID-19/index.html

The CDC has daily updates on coronavirus in the United States at https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html#investigation

Opioid Addiction Treatments

Opioid abuse and dependence affects nearly 5 million people in the United States and leads to around 17,000 deaths every year. Opioid addiction can involve prescription drugs (oxycodone, hydrocodone) or illegal drugs like heroin, or a combination of these.

Treatment options to help addicts recover include the following medications:

  • Methadone: methadone is an opioid also and is typically used to help addicts to stop using heroin. Methadone therapy is intended to reduce withdrawal symptoms and cravings, not to get the patient high or substitute one addiction for another. It replaces heroin with a pharmaceutical product, but with some clear advantages. It is longer acting and can be given once daily. This helps patients to have a more stable lifestyle, with less criminal activity, needle sharing and other behaviors that contribute to morbidity and mortality among addicts. Unlike street drugs, it is a standardized dose and does not contain adulterants or contaminants. Methadone is only available at specialized methadone clinics for the treatment of addiction. A retail pharmacy may stock methadone but can only dispense it for treatment of pain, not for opioid addiction.
  • Buprenorphine/naloxone (Suboxone, others): Buprenorphine is an opioid also, but unlike other opioids, it is a partial agonist, meaning it causes less of a high, and has a ceiling effect so that taking larger doses will not have additional effects. This makes it a safer option than methadone, which can be lethal in an overdose. Buprenorphine stops withdrawal and cravings. Naloxone is an opioid antagonist (a.k.a. Narcan) and it blocks the effects of opioids. However, naloxone is very poorly absorbed when taken sublingually (as Suboxone) and has been added to these products to alleviate concerns that the tablets would be dissolved and injected intravenously. Since naloxone is highly effective when given intravenously, injection of Suboxone or these other products would not result in a “high” for the user, as the naloxone would block the effects. Products like Suboxone are not as highly restricted as methadone and can be dispensed at retail pharmacies. However, physicians have to be certified to prescribe Buprenorphine products and can only treat a limited number of patients. A once-monthly injection of Buprenorphine is available called Sublocade, and a Buprenorphine implant that lasts for 6 months is also available. Read more about that here.
  • Naltrexone: Naltrexone is an opioid antagonist like naloxone but is longer acting. It blocks the effects of opioids. This type of medication is harder to initiate since it requires the patient to do a complete detoxification from opioids before use. If given to a patient who is still opioid dependent, it will cause withdrawal symptoms. This medication is a good option for patients who are off opioids and are at risk of relapse. It can be useful for patients who have tapered off of methadone or Buprenorphine. Naltrexone comes in a once daily tablet or a monthly injection. Naltrexone can also be used to treat alcohol dependence.

For more information:

https://emedicine.medscape.com/article/287790-treatment

https://www.drugabuse.gov/publications/effective-treatments-opioid-addiction/effective-treatments-opioid-addiction

To find a treatment program: https://www.hhs.gov/opioids/treatment/index.html

New Treatment for Severe Asthma

Tezepelumab is a new asthma treatment that has been granted Breakthrough Therapy Designation by the FDA. This designation helps to expedite the development and regulatory review of medications that potentially treat serious conditions. About 10% of patients with asthma may have severe asthma which can adversely affect their quality of life and is often debilitating or even fatal.  While there are several treatments available for asthma already, patients who suffer from severe asthma are often reliant on medications like oral steroids (e.g. prednisone) which can have severe side effects when taken long term.

Tezepelumab is a monoclonal antibody and it works by blocking thymic stromal lymphopoietin (TSLP), which is a cytokine that is produced in response to environmental or inflammatory stimuli. TSLP is present in higher concentrations in the airway tissues of patients with asthma, and higher levels are correlated with greater disease severity. TSLP is a component of several inflammatory pathways and blockade of these pathways can prevent asthma exacerbations and reduce the severity of asthma symptoms. Clinical trials have shown a reduction of about 60-70% in the number of asthma exacerbations with different doses of tezepelumab. Dosing will likely be every 2-4 weeks, and like other monoclonal antibodies, tezepelumab is given by injection. Common side effects include headaches and nasopharyngitis.

Other monoclonal antibodies used for asthma (e.g. Xolair, Dupixent) work by targeting different biochemical pathways. So for patients who have not achieved good control of their asthma with currently available medications, this will provide another potential option if it is approved.

For more information:

https://www.specialtypharmacytimes.com/news/fda-grants-breakthrough-therapy-designation-to-tezepelumab-for-severe-asthma

https://www.nejm.org/doi/10.1056/NEJMoa1704064

Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic condition that causes inflammation in the esophagus and can lead to problems with swallowing and food impaction, where food becomes stuck in the esophagus and the patient requires medical attention to remove it. This condition was first recognized in the 1990s and has been increasing in incidence and prevalence since then. Once considered a rare disease, it is now becoming far more common.

Most patients with this condition have a family history of allergies or asthma, and often have food allergies that aggravate the condition. Unlike some food allergies though, patients with EoE often have a delayed reaction to the food they are allergic to. Instead of developing hives or anaphylaxis right after ingestion, patients will develop swelling in the esophagus hours, or even days later. This makes it difficult to identify the allergen, so allergy testing may be needed.

Treatment of EoE typically involves removing problematic foods from the diet. Common food allergens like eggs, soy, peanuts, shellfish, wheat, and dairy may be removed from the diet to see if the condition improves. Patients with severe difficulty swallowing, or food impaction may require endoscopic dilation to relieve symptoms. This involves using a device to stretch open the esophagus to allow food to pass.

Pharmacological therapy for EoE may include use of a proton pump inhibitor to prevent stomach acid from damaging the esophagus, or having the patient swallow small amounts of a corticosteroid to reduce inflammation. This is typically done using a steroid asthma inhaler and having the patient spray it in the back of the throat several times and then swallow. Pharmacists should be aware that these medications may be used for this condition also, in addition to their use as asthma therapy.

For more information see https://www.aaaai.org/conditions-and-treatments/related-conditions/eosinophilic-esophagitis or  https://www.ncbi.nlm.nih.gov/pubmed/30364207

Sunscreens

When I worked for the poison control center, we would often get calls about children ingesting sunscreen products. Many of them contain active ingredients that are salicylate compounds (similar to aspirin) and if ingested in a sufficient amount, could cause toxicity. Fortunately most children did not eat enough to cause a problem.

However, a recent study suggests that ingredients in sunscreens, including oxybenzone, avobenzone, octocrylene, and ecamsule are absorbed through the skin in larger amounts than expected, even when used as intended. The concentration also increases over time, indicating drug accumulation. While this may sound like a cause for concern, the effects of the accumulated drug in the amounts measured is unknown. Further studies are needed to determine the clinical significance of these findings.

The FDA is also taking a closer look at sunscreen safety. New regulations may require updated testing and labeling. Two ingredients, zinc oxide and titanium dioxide, are considered to be the safest.  Two other ingredients, PABA and trolamine salicylate, which are not marketed in the United States, are considered unsafe. There are several other sunscreens for which there is not enough information to determine safety. These include cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone. These ingredients will be coming under increased scrutiny by the FDA. This doesn’t mean they are not safe, only that more information is needed.

For a safe day in the sun, long sleeves, hats, sunglasses and shade are always a safe bet, and sunscreens that provide a physical barrier (zinc oxide, titanium dioxide) are the best choice for now.

https://www.medscape.com/viewarticle/912651

https://www.medscape.com/viewarticle/909428#vp_1

Metformin and the Microbiome

Most people familiar with the diabetes drug metformin know that it can have some unpleasant effects on the digestive tract including nausea and diarrhea. Long term use of the drug can also lead to a deficiency of vitamin B-12 due to decreased absorption of the vitamin.

Studies also suggest that metformin can alter the composition of the microbiome and enhance the growth of a bacterium called Akkermansia muciniphila  and other bacteria that produce short-chain fatty acids (SCFAs). SCFAs like butyrate, propionate, and acetate have been associated with a decrease in obesity and insulin resistance, and can protect against colon cancer.  An abundance of A. muciniphila has been associated with less abdominal fat, lower blood sugar levels and improved insulin sensitivity. This may in part explain how metformin can help with weight loss and blood sugar control.

While there are many probiotic products available, they do not typically contain Akkermansia. This is likely because the bacterium was only recently discovered, and the ideal amount needed in the microbiome is not yet clear.

For people not taking metformin who want to increase levels of beneficial A. muciniphila, consumption of navy beans has been shown to be effective. More here

SCFAs, especially butyrate can be found in supplements or in a healthy diet. Cow’s milk is a good source of butyrate, and high-fiber foods will increase butyrate during fermentation in the intestines by gut microbes. More here

Sources:

https://www.ncbi.nlm.nih.gov/pubmed/27999002

https://www.ncbi.nlm.nih.gov/pubmed/29231905

G6PD Deficiency

Glucose-6-phosphate dehydrogenase deficiency is an inherited enzyme deficiency that affects around 400 million people worldwide. It is more common in people of Mediterranean, African, or Asian descent. This gene has persisted in those regions due to the fact that it provides some protection against malaria. In the United States it affects about 10% of African American males. Babies with this condition may have jaundice at birth.

Patients with this enzyme deficiency have less protection against oxidative stress, due to decreased amounts of NADPH (nicotinamide adenine dinucleotide phosphate) which protects red blood cells. The degree of the deficiency determines the clinical symptoms. Patients with a minor deficiency may not have any symptoms.

Most people who have this condition do not require treatment but they will need to avoid certain foods and drugs or they may develop hemolysis, a breakdown of red blood cells which leads to anemia.

Pharmacists and other health care providers should be aware of medications that should be avoided by patients with G6PD deficiency. These include dapsone, sulfa drugs, nitrofurantoin, flutamide, methylene blue, phenazopyridine, chloroquine, and NSAIDs.

People should also avoid exposure to moth balls containing naphthalene.

Patients should avoid eating fava beans, also known as broad beans or pigeon beans. Sensitivity to fava beans is more common in G6PD patients of Mediterranean descent.

If anemia does develop, it is typically self-limiting and resolves in 1-2 weeks. More severe cases may require a blood transfusion.

Symptoms of hemolysis include paleness, dark urine, fatigue, enlarged spleen, and rapid heart rate. A blood test can be used to diagnose G6PD deficiency.

 

Sources:

https://emedicine.medscape.com/article/200390-overview

https://www.aafp.org/afp/2005/1001/p1277.pdf

Inhaled Insulin

Inhaled insulin seemed like a great idea the first time around because everybody liked the idea of not having to give injections every day. It seemed especially promising for use in children or those with a phobia of needles. It sounded like it would be easier to administer than injections which required alcohol swabs, sharps containers, and a certain amount of privacy.

Exubera™ came to market over 10 years ago but sales of the product never really took off. It required a large device to aerosolize the insulin, the dosing was not as flexible as with injectable insulin, and it turned out to have some concerning pulmonary side effects, including declining lung function and a possible link to lung cancer. It had to be used in conjunction with long-acting injectable insulin, so patients still needed injections. The product was withdrawn from the market within 2 years.

In 2014, another inhaled insulin called Afrezza™ was approved by the FDA. This one appeared to have some advantages over its predecessor, such as a smaller device and easier to convert dosing. But the concerns about lung problems persisted. Introducing insulin which has growth factor properties directly into lung tissue could increase the risk of lung cancer. Although clinical trials have not been large enough to determine cause and effect, this is worrisome for patients and prescribers alike.

With several new injectable insulins becoming available in the last few years, patients have several options available, and the future of inhaled insulin is unclear. Patients with severe needle phobia seem to be the most likely market for this product.

Other non-injectable options may be coming, though. See my post on oral insulin.

More info at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001220/ and https://www.afrezza.com/