What are the dangers of taking Mucinex DM and Tylenol simultaneously?

Taking guaifenesen and dextromethorphan (Mucinex DM) with acetaminophen (Tylenol) should not pose a risk of drug-drug interactions, since the metabolism (clearance) of these products do not directly interfere with each other:

Guaifenesin/Guaiphenesin

Use as expectorant (thins mucus to make cough productive)
Metabolized via hydrolysis: Unknown if metabolism via liver enzyme cytochrome P450 (CYP450)
Dextromethorphan

Use as a cough suppressant (anti-tussive) and pseudobulbar affect (uncontrolled crying/laughing)
Metabolized via liver, CYP450 2D6
Acetaminophen/Paracetamol

Use to reduce fever and pain
Metabolized via liver, CYP450 2E1
The main dangers in these medications have to do with excessive concentration of the drug in your body, i.e. overdosing.

Overdosing on dextromethorphan causes breathing problems including no breathing, blurred vision, coma, hallucinations, gastrointestinal spasms (see Dextromethorphan overdose: MedlinePlus Medical Encyclopedia).

Overdosing on acetaminophen causes liver damage serious enough to require transplantation or result in death. You should not take more than 4 grams or 4000 mg per day. Brand name Tylenol comes in doses of 500mg each pill or caplet, which means you should not take more than 8 pills or caplets per day. If you take 2 pills or caplets each dose, you can only take 4 two-pill doses each day to stay on the safer side of liver damage.

Fortunately, guaifenesin toxicity is relatively low, but doses for an adult should not exceed 2400mg per day.

Mucinex DM comes in “regular” and “maximum” strength. Regular strength contains 30mg dextromethorphan hydrogen bromide (HBR) and 600 mg guaifenesin, which you can take 1 or 2 pills (2 pills yield 60mg dextromethorphan 1200mg guaifenesin) every 12 hours. Maximum strength contains 60 mg dextromethorphan and 1200mg guaifenesin, which you can take 1 tablet every 12 hours.

Source: Cough & Chest Congestion Medicine | Mucinex®

You can calculate which is cheaper, by buying either maximum strength and taking 1 pill every 12 hours, or regular strength but taking 2 pills every 12 hours. People tend to prefer swallowing 1 pill versus 2 or more, so less pills per dose is better for patient compliance.

Do Mylan shareholders want the CEO to keep raising the price of the EpiPen?

Do Mylan shareholders want the CEO to keep raising the price of the EpiPen? We don’t know yet.

Investors like a company to deliver positive earning results and increased guidance, and the recent negative public opinion has given investors a reason to sell, which was what happened. Currently $MYL is in “oversold” territory.

Mylan 1 year and 5 year trends:
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Keep in mind that 68% of Mylan is institutionally owned. Thus the market makers’ decisions will determine whether “shareholders” truly want the CEO to keep raising prices of the EpiPen. Retail (individual) investors’ outrage makes little difference to $MYL stock price, unless you happen to be an individual who owns millions of shares of $MYL.

I suspect that there is a sweet spot that is not being discussed, which is, the institutional investors want to ensure that the EpiPen continues to dominate the market (which is temporarily the case, given the set backs of potential major competitors) but also not be priced to the point where backlash from the reimbursement side triggers costly events.

If $600 is too much for public opinion to stomach, what about $500? $400? It’s not so much about what the “real” price ends up being on the consumer-side, but the publicity around the price itself, as well as the defense of the price by a CEO who hasn’t been successful pitching the coupon/assistance angle. That’s about as effective as a U.S. private university saying, “Sure, our tuition is $65,000 a year, but our students almost never pay full price!!!”

SOMEONE is absorbing the escalating cost of a life-saving product, and we’ve been around the block long enough to know that at the end of the convoluted cost justification conveyor belt, we consumers will end up getting bitten on the butt.

Entities investing in businesses can claim an interest in public good, but only based on the extent that the cost/risks from actual (lawsuits, sanctions, blacklists) or perceived (bad PR) harm not exceed the revenues earned from pushing-moral-envelope decisions.

Once that risk begins to overshadow the rewards, you will see major shareholders send a message by selling $MYL shares. Then we can say for sure whether shareholders want the CEO to keep raising prices. Even Turing and Valeant had their glory days of astronomical stock prices, so you can’t say that shareholders aren’t enamored by questionable business practices, at least in the short term.

It’s all about risk:reward.

Update 8/29/2016

Within a week of the public outrage, Mylan will Launch Cheaper Generic EpiPen Alternative. Sounds like a good response, until you consider the fact that Mylan’s ability to launch this generic version in “several weeks after labeling revisions” means Mylan has always had within its capacity to offer a more affordable product (keep in mind, the generic version is still a 300% price hike from the original $100 tag). When was Mylan ever going public with this generic?

Also in question is 1) the growing public awareness of the CEO’s 600%+ hike in compensation that is being linked to the company’s pricing “strategy” and 2) less public awareness of the CEO selling 100,2000 shares of company stock at $50/share for a gross $5,010,000 after the earnings report, but before the price hike frenzy (SEC FORM 4). You can’t convince me that any executive shrewd enough to get to a C-level position can’t foresee the possible public backlash to a 600% price hike of a cheap drug delivered in the medical device that is really the main “product”.

The fact that Mylan did this in response to negative publicity reinforces the public perception that the pharmaceutical industry does indeed have “affordable alternatives” but chooses to withhold them to the public to rake in more profits. Even though reality is what Bruce Booth wrote in Forbes (Innovators vs Exploiters: Drug Pricing And The Future Of Pharmaforbes.com), where differential pricing exists for the industry to offset the steep discounts in other countries by making “countries that can pay”, pay much, much more.

The average consumer is not going to care to understand the complex pharma industry supply chain or convoluted regulatory maneuvers. The consumer knows that healthcare is at a tipping point that somehow hasn’t been tipping in the right direction, and industries like pharma spending a lot of money lobbying and advertising. More and more, social media is enabling consumers to coalesce into groups and transform into activist voices that can change how companies make decisions.

This means the pharmaceutical industry should start paying attention to actually educating consumers on the brutal realities of opaque drug pricing versus perennially showcasing the bloating belly of “cost of discovering and bringing drugs to market.” Let’s face it, that argument has not convinced the public on why drugs cost so much, and it’s a failed strategy. The industry needs to spend money on what actually works to engage consumers, not on new versions of the same graphs that had thus far convinced few and far between.

Theranos’ AACC Presentation: Not the Reboot We Were Hoping For

Move over, Edison: here comes miniLab.

And yet: “Every piece of technology they presented has been known for many years, and exists in other platforms largely in the same configuration, or in some cases in much more compact form in competitor’s platforms.” ~ associate professor in U. Washington’s dept of laboratory medicine.

Data has not been independently verified.

Holmes did not clarify that the 11 tests she presented would require at least 3-4 pricks if each prick yields only 160-uL amounts.

https://www.wsj.com/articles/theranos-founder-elizabeth-holmes-introduces-new-blood-testing-device-1470089582

https://www.wired.com/2016/08/theranos-chance-clear-name-instead-tried-pivot/

Killing Zika Virus Carrying Mosquitoes with Gene Drives?

Genetically engineering out the lives of pests is not a new idea. The idea of leveraging sexual reproduction to pass specific gene changes (mutations or alterations) through entire populations to control pests has been proposed as far back as the 1940s, for example, A Strain of the Mosquito Aedes aegypti Selected for Susceptibility to the Avian Malaria Parasite Plasmodium lophurae.

Evolutionary geneticist Austin Burt was credited with the method of cutting DNA to reduce populations of disease-spreading species and the associated idea of “Gene drives”. The central idea behind a gene drive is to ensure that the engineered module stands a high probability of being passed onto offspring, such that the genetic module can be spread through the population. We can “drive” a genetic mutation into an entire population.

“How do we do this?”

Imagine if we can genetically engineer the virulence out of mosquito bites — nay, let’s engineer the future lives out of an entire species of the worst offenders (these would be the aegypti mosquitoes) — and free our communities of chemical pesticides! Kill the pests but spare our environment!

That is what Oxitec is working on. The company is harnessing a pathway that has been explored for killing cancer cells to genetically engineer male aegypti mosquitoes. Male aegypti mosquitoes live long enough to mate with female aegypti mosquitoes in the wild. Males pass along what amounts to a ticking time bomb genetic sequence to their female partners. Their offspring will then carry these gene sequences that produce death-causing proteins.

Female aegypti mosquitoes are the ones that bite and deposit diseases in hosts. Thus rather than working on fatality-causing mutations where an aegypti mosquito embryo won’t even see the light of day, Oxitec wants the males mosquitoes to mate with the existing biting wild female population. Offsprings will die before adulthood due to the inherited vulnerability or will be too weak to survive the normal assaults of nature.

“Should we do this? How far should we do this?”

Along with questions of possibility and feasibility comes questions of ethics and responsibility.

What are the ethics of genetically extinguishing entire species, even if we’re talking about a loathed species like the aegypti mosquitoes? You will hear bioethicists talk about the impact on the natural food web and the ripple effect of employing such technology (i.e. “Today, mosquitoes. Tomorrow, other species maybe even certain humans?”)

Additionally, one can argue that the very situations fertile for cultivating diseases are not fixed by genetically fixing pests. How does genetically engineering mosquitoes fix the slums and ghettos in which pests and disease carrying insects establish and thrive? How do we know that another species won’t take the place of one that we genetically extinguished, because the very conditions of poverty remain?

Questions about genetically engineering away virulence and pestilence are complex, and reach beyond what is merely scientifically possible.

We need to consider the law of unintended consequences, and these are complex questions of consequences that are difficult for us to imagine, until we’ve done it.

Then, do we do it? Should we do it?

How Antibiotics Work

Antibiotics work according to the mechanism of action (what the drug “targets” in microbes or how the drug “works” in the microbe) that is driven by the drug’s distinguishing chemical structure.

Chemical structures also define the “classification” of antibiotics. If you hear doctors talk about “macrolides” versus “quinolones”, they are talking about families of drugs (not “one” specific drug) and they are referring to the way each family of drugs targets microbes.

When you hear about “generations” of an antibiotic, this means the chemical structure of the current drug has been modified (changed) somehow. These changes are designed to improve the action of the drug, especially when the bacteria have evolved to resist the original drug.

A well known example is Penicillin resistance. Overuse of penicillin resulted in widespread bacterial resistance to this drug. If I went to the doctor today and the doctor decided that a beta-lactam based antibiotic was appropriate, the doctor may prescribe amoxicillin or one of the newer generation cephalosporins versus the original penicillin. That’s because the doctor is thinking the bacteria in my body will probably laugh at penicillin and a “newer” penicillin (like amoxicillin) may be needed.

Why We must complete the ENTIRE course of antibiotic therapy

One of the biggest problems in antibiotic resistance, besides antibiotics being over-prescribed, is patients stopping their medication as soon as they start feeling better instead of finishing their entire course (taking ALL pills prescribed by the doctor).

Imagine your body is a kingdom and your immune system as a fortress/defense system. Your kingdom has undergone an invasion. Taking antibiotics is similar to giving your immune system a much needed weapon to defeat the invaders.

A full course of antibiotic therapy aims to kill off as many invaders that have infiltrated your kingdom within as short amount of time as possible, so that your defense system can take care of the rest, and to ensure that ALL the invaders are killed.

People sometimes stop taking the antibiotic when they start feeling better (“Oh, I’m already feeling better”) or for another reason (“hey, maybe I should save these couple of pills, just in case, for next time”). The problem is that there may be a few invaders that have thus far evaded the antibiotic response, and these will be the invaders who will come back with a vengeance, literally.

Your feeling better has do to with most of the invaders being killed off, but the few that have escaped being killed are buying time to adapt and evolve… to become smarter against your defenses.

Antibiotic resistance arises from the ones that have been allowed to escape because the host (you) decided “All is well, call off the troops!” and giving the invaders time to learn how to better take you down the next time there is an opportunity.

Based on the way each antibiotic family targets microbes, the drugs in that antibiotic family may either kill (bactericidal) or stall the growth of (bacteriostatic) microbes.

This is where we get into the specifics of “how” an antibiotic works. Antibiotics aim to kill by:

  • Targeting a specific feature of bacteria
  • Targeting the reproductive process of bacteria
  • Targeting a critical chemical pathway in bacteria (especially protein synthesis)
  • Overcoming bacteria’s evolved mechanisms of resistance (for example, bacteria that have evolved pumps in their membranes to “pump out” drugs)

Targeting a Specific Feature of Bacteria, Reproduction, or critical process (typically making proteins or “protein synthesis)

Antibiotics that target gram positive bacteria will disrupt the chemical process critical to making the thick peptidoglycan wall (the thick wall is what holds the “gram stain” that allows us to visually identify the “gram positive” bacterial strain).

However, if the bacteria has a thin peptidoglycan wall (this then won’t show up as bright violet stains on the gram stain, making this bacteria a “gram negative” type), then an antibiotic that targets that wall won’t do much damage.

Instead, you’d need an antibiotic that targets a specific feature of gram negative bacteria or target a critical process like protein synthesis. For example, the antibiotic can cross the gram negative bacteria’s cell wall (but are blocked by gram positive bacteria’s peptidoglycan layer) to stop protein synthesis, which stops many critical machinery in bacteria.

Antibiotics that target the bacterial reproduction prevents new bacteria from being produced. This gives your body a fighting chance to go over the existing microbes.