For Clinicians | Controlled Substance Emergency Refill Rules

For Clinicians | Controlled Substance Emergency Refill Rules: A Pharmacist’s Q&A

By Dr. Jamie Wilkey, PharmD — Director of Clinical Strategy, Jase
Medically reviewed and edited by Kristen Carpenter, PA-C

Hi again, it’s Jamie, your pharmacist. 

Here at Jase, we really like to help people be prepared for disasters, whether they be natural or supply chain or just being far from medical care. Most of the time we’re talking about regular medications, blood pressure and diabetes, etc.  But those aren’t the only medications that are really important to patients.

Today we’re talking about controlled substances, because they are much more complicated in a disaster. The same rules don’t apply for them as they do for the regular, or legend, medications. So here’s how these controlled substances generally work, what the different categories mean, and the problems I see go wrong most often when someone can’t get one filled.

One caveat: each state has different rules, so this is an overview and in no way comprehensive. Your local pharmacist knows your state’s rules very well and can help you the most.

Before we start, three things. 

  1. We are not telling anyone to get extra opioids or extra stimulants. We never will, and federal law mostly doesn’t allow for it anyway. 
  2. Jase does not sell controlled substances at all, not one, in any kit or any add-on. 
  3. This class gets complicated faster than anything else in the medicine cabinet, which is exactly why we’re covering it instead of skipping it like most preparedness writing does.

“What schedule is it?”

This is the first question I ask, and most patients have no idea their prescription has a number, or schedule as we call it, attached to it. Here’s how those drug classes work:

  • Schedule II is the stimulants, oxycodone, hydrocodone, morphine, methadone. No refills, ever. That’s federal law, not a pharmacy policy. But a prescriber can write two or three prescriptions at the same visit, up to a 90-day total supply, each with a “do not fill until” date on it.¹ That’s federal too, where state law allows it.
  • Schedule III through V is buprenorphine, most benzodiazepines, tramadol, pregabalin. Those can carry refills. They can be transferred between pharmacies if both are open and willing to transfer. In a lot of states a pharmacist can step in during an emergency here.
  • There is a Schedule I, but I’m not writing about it here because these meds are not allowed to be dispensed in a pharmacy in any state ever. Think heroin or LSD, etc. 

Two bottles can sit in the same drawer in the same house for the same patient and be in completely different situations. The Rx label won’t tell you which class of medication the drug is, either.

“Which ones are actually dangerous to stop?”

Benzodiazepines are the medical emergency. Stopping abruptly in a physically dependent patient can cause seizures and delirium, and that includes patients on a therapeutic dose who have never had a seizure in their life. ASAM and nine other societies published a tapering guideline in June 2025 that says outright not to discontinue abruptly in anyone likely to be dependent.²

Opioids are the opposite problem. The withdrawal is miserable and rarely lethal on its own, though it isn’t benign in pregnancy. The danger is the restart. Tolerance drops within days, and the dose that was routine two weeks ago can be the one that stops their breathing. So the plan has to cover going back on, not just running out.

Stimulants aren’t physiologically dangerous to stop, and CDC issued a health advisory about it anyway.³ In June 2024 a federal indictment against a large subscription telehealth company put 30,000 to 50,000 adults at risk of losing their ADHD prescriber, in all 50 states, more or less at once. CDC’s worry wasn’t withdrawal. It was that people go looking, and what’s on the street pressed to look like Adderall is frequently fentanyl.

Only the benzodiazepines are likely to hurt someone in the first week. The other two hurt them later, and need to be a part of the patient’s post-disaster care plan.


“Can another pharmacy just fill it?”

Sometimes. It depends on whether it’s already been filled at another pharmacy.

If the prescription is still sitting at a pharmacy unfilled, a rule that took effect in August 2023 lets it move.⁴ Any electronic controlled substance prescription, Schedule II included, can be transferred one time to another retail pharmacy. The patient has to ask, and has to name the pharmacy they want it sent to. The two pharmacists handle it directly. That’s it. One transfer, and the prescription has to still be electronic and unfilled. And both pharmacists have to agree to it. I know in practice still in mid-2026 not all pharmacies are connected online, so from my experience in Utah there’s about a 45%ish success rate between pharmacies in the same state. It’s less successful as you move out of state. I’m sure it’ll improve every month as time marches on, but that’s where we are now. 

If it’s already been filled and you’re looking for the refills, that’s a different rule, and Schedule II is out because there are no refills to transfer. For Schedule III through V, refill information can be transferred once, unless the two pharmacies share a real-time database.⁵ And again, both pharmacists must agree. If a pharmacist doesn’t feel comfortable dispensing it they can refuse the prescription. 

“Can’t the pharmacist just give me a few days’ worth?”

For a lot of medications, yes. Most states let a pharmacist dispense an emergency supply when the prescriber can’t be reached, and many widen that once a governor declares an emergency. How much and under what conditions varies state to state.6

Schedule II is almost always carved out, and the reason is structural. Those laws work by letting a pharmacist extend an existing prescription, and Schedule II has no refills to extend.

There is a federal path for Schedule II. In an emergency a pharmacist can dispense a Schedule II on a prescriber’s spoken authorization, limited to the amount needed to get through the emergency.7 The pharmacist writes it down on the spot, and the prescriber has seven days to send a written prescription marked “Authorization for Emergency Dispensing.” Again, it is still within the pharmacist’s purview to choose to fill it or not if a prescriber calls the emergency Rx in. 

Methadone runs on two different systems depending on what’s being treated. Prescribed for pain, it’s an ordinary Schedule II prescription and everything above applies. Prescribed for opioid use disorder, it can only be dispensed by a federally certified opioid treatment program.⁸ Not a retail pharmacy, not in an emergency, not with a prescriber on the phone. So a displaced patient calling pharmacies is wasting the day. What they need is another certified program willing to dose them temporarily, which programs already do routinely for people who travel.

The bottom line

Every option in this article runs through a prescriber someone can reach. That’s the part that can fail first in a real life emergency. 

For every patient on a controlled substance who’s worried about this and wants to plan ahead with you, decide now what happens if they can’t fill for a week, and talk it through together. Which schedule is it? Does it taper or wait if it can’t be filled? Who authorizes an emergency dose, and at what contact number?

That’s what appropriate medical preparation looks like for a class where preparation can’t mean an extra supply on the shelf. None of this replaces the relationship these patients already have with you, and for this class nothing could. We’ll keep publishing how we work these questions out. For questions in your own state pick up the phone and call your local pharmacist. They are the experts here and happy to help.


Sources

  1. 21 CFR 1306.12, Refilling prescriptions; issuance of multiple prescriptions. Schedule II refills prohibited under (a). Paragraph (b) permits multiple prescriptions totaling up to a 90-day supply, each carrying written instructions on the earliest date a pharmacy may fill it. https://www.ecfr.gov/current/title-21/chapter-II/part-1306/subject-group-ECFR8588b52940237ef/section-1306.12
  2. American Society of Addiction Medicine et al., Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits. Journal of General Internal Medicine, June 2025. ASAM with nine partnering societies, modified GRADE methodology. Recommends against abrupt discontinuation in patients likely to be physically dependent, with initial reductions of 5 to 10% every 2 to 4 weeks and not exceeding 25% every two weeks. https://link.springer.com/article/10.1007/s11606-025-09499-2
  3. CDC Health Advisory CDCHAN-00510, Disrupted Access to Prescription Stimulant Medications Could Increase Risk of Injury and Overdose. June 13, 2024. https://www.cdc.gov/han/2024/han00510.html
  4. DEA final rule, Transfer of Electronic Prescriptions for Schedules II-V Controlled Substances Between Pharmacies for Initial Filling. Federal Register, July 27, 2023, effective August 28, 2023. One-time transfer at the patient’s request, prescription must be unfilled and remain electronic, communicated directly between two licensed pharmacists. https://www.federalregister.gov/documents/2023/07/27/2023-15847/transfer-of-electronic-prescriptions-for-schedules-ii-v-controlled-substances-between-pharmacies-for
  5. 21 CFR 1306.25, Transfer between pharmacies of prescription information for Schedules III, IV, and V controlled substances for refill purposes. One-time basis only, unless the two pharmacies share a real-time online database. https://www.ecfr.gov/current/title-21/chapter-II/part-1306/subject-group-ECFRe4ae2bfb4eae102/section-1306.25
  6. Healthcare Ready, A Review of State Emergency Prescription Protocols. https://healthcareready.org/a-review-of-state-emergency-prescription-protocols/
  7. 21 CFR 1306.11(d), Requirement of prescription. Emergency dispensing of a Schedule II on a practitioner’s oral authorization, limited to the quantity needed for the emergency period, with a written prescription marked “Authorization for Emergency Dispensing” delivered within seven days. https://www.ecfr.gov/current/title-21/chapter-II/part-1306/subject-group-ECFR8588b52940237ef/section-1306.11
  8. 42 CFR Part 8, Medications for the Treatment of Opioid Use Disorder. No program may dispense methadone for opioid use disorder without SAMHSA certification. https://www.ecfr.gov/current/title-42/chapter-I/subchapter-A/part-8

 

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For Clinicians | Why Drug Shortages Happen and How Long They Actually Last

For Clinicians | Why Drug Shortages Happen and How Long They Actually Last

By Dr. Jamie Wilkey, PharmD — Director of Clinical Strategy, Jase
Medically reviewed and edited by Kristen Carpenter, PA-C

Hi, I’m Jamie. I’m also a pharmacist. I’ve spent more than ten years behind the pharmacy counter, and I’ve helped thousands of patients and prescribers work around a drug shortage. Unfortunately, I know a lot about drug shortages and what a pain they can be. 

Drug shortages peaked in 2024, when 323 of them were active at once. We’re lower now, but 227 drugs are still in shortage as of mid-2026.¹ So I thought it would be fun to do this one question-and-answer style: what a shortage actually is, why they happen, what your pharmacist can and can’t do, and what you should know as a prescriber to help your patient through one.

These are the questions I get the most, and my answers.

“Why do drug shortages keep happening?”

Most of the time nobody tells us. When the University of Utah Drug Information Service asked manufacturers why a drug went short in 2025, 59% either didn’t know or wouldn’t say.¹ Independent analysis fills in some of that gap and points to manufacturing quality problems as the largest single driver.² A problem turns up at a plant, the manufacturer slows or halts production to fix it, and supply that was already thin disappears. Just under half of this year’s new shortages came from sole-source products, where one manufacturer is the whole supply.¹Most of the drugs that go short are generic sterile injectables, hard to make and sold for almost nothing because hospitals buy on price.³

Which explains why a shortage doesn’t ease just because the whole country needs the drug. In most markets, high demand pulls in new suppliers. Here in the pharmacy manufacturing world it barely does. A company that wanted to start making a short drug needs its own FDA approval for that product at that specific plant, plus tech transfer and validation batches on a sterile line. That’s a multi-year project ending in a product that sells for pennies, and the shortage may be over before they arrive. So nobody comes and medication stays short sometimes for whole years.

The drug comes back when that manufacturer fixes what the FDA found, revalidates the line, and passes reinspection. That clock runs on remediation, not on how badly your patient needs it.

“How long do drug shortages last?”

Way too long. HHS looked at every shortage between 2018 and 2023 and found a median duration of 2.55 years.⁴ Not weeks or months that you’d mentally expect. Years.

The split by dosage form is important here for you healthcare providers. Oral drugs ran a median of 1.59 years, injectables 4.60.⁴ Three years into a shortage, 8.1% of oral products were still short. For injectables it was 64.6%.⁴ So if what your patient needs is a tablet, waiting it out is at least a real strategy. If it’s an injectable, the odds are close to two in three that it’s still short three years from now.


“So what does this mean for your patients?”

Here’s the weird part: a drug in shortage is usually not 100% unavailable. Shortage means supply isn’t meeting demand, and day to day that looks like dribs and drabs are coming into the pharmacy. Some weeks the wholesaler releases a little, some weeks nothing. One strength ships while another doesn’t. Most of the time the drug goes on allocation, so a pharmacy can order only a fraction of what it normally buys, based on its own purchase history.

Which is why two pharmacies in the same town tell your patient different things in the same week, and both are being truthful for their situation. One got a partial shipment Tuesday. The other is capped well below what it needs and spent its allocation on patients already established on the drug.

So when a pharmacy says they can’t get it, that’s true, and it’s also not the whole story. It’s this pharmacy, this week, this strength.

“But the FDA site says there’s no shortage…”

Great question. And it is confusing here! Two national lists intentionally count different things. FDA calls it a shortage when nationwide supply isn’t meeting current or projected demand. ASHP lists any shortage a practitioner reports and it confirms, down to the specific manufacturer, strength, and vial size.7 So a drug can be truly unavailable from the manufacturer your patient’s pharmacy buys from and never show up on FDA’s list, because nationally the supply is holding.

Same reason this year’s headline numbers look like they contradict each other. Only 89 new shortages started in 2025, the fewest since 2006.⁵ Active shortages climbed anyway, three quarters in a row.⁶ Fewer beginnings, yes, but the existing backlog isn’t clearing.

So when your patient says the FDA site shows their drug isn’t short, they aren’t wrong. They’re reading the answer to a different question.

“What can the pharmacy actually do?”

Most of this is our job as pharmacists and pharmacy technicians, and it starts before we call you. We’re checking what the wholesaler will release, calling nearby locations, pulling the manufacturer’s estimated resupply date, and working out which substitution is actually available today. By the time your phone rings, we’ve usually ruled out the easy options and we’re calling because the remaining one needs your signature.

Here’s what we’re working through behind the scenes:

  • Another manufacturer. For a generic we can usually source a different labeler without calling you at all, unless you wrote it brand-specific or dispense as written.
  • Another strength at the same total dose. Two 10 mg tablets instead of one 20 mg. Depending on your state, we can often do this without a new prescription.
  • Another formulation. A capsule substituted for a tablet, etc. Requires a new Rx from you.
  • A transfer (as long as it hasn’t been filled yet). Since 2023, even controlled substances can move. An electronic prescription for a Schedule II through V drug can transfer between retail pharmacies one time, at the patient’s request, pharmacist to pharmacist, where state law allows.⁸

One caution on the resupply date we quote you. It comes from the manufacturer and it moves. Treat it as an estimate with the best information we get…. not a promised delivery date.

“How do I work with the pharmacy most efficiently on this?”

Your pharmacist will probably reach out with a substitution already in mind, or handle it without you when we’re able to. That’s going to be more effective than sending over a best guess that may well be out of stock too.

Controlled substances are where the order of operations flips. A Schedule II prescription can’t be refilled, so every fill is a new prescription, and you can’t scatter one across three pharmacies to see who has stock. ADHD stimulants are the poster-child drug classes most of us have lived through recently.⁵ So have your patient call around first and confirm the exact drug, strength, and quantity is physically on the shelf of a pharmacy, then send the prescription to that pharmacy. Some won’t confirm controlled stock over the phone, so your patient may have to walk in and ask. Either way it beats your staff calling every pharmacy in the county. And if a prescription is already sitting at the first pharmacy, ask them to delete it so you don’t leave a duplicate out there.

The bottom line

Shortage guidance exists, but look who it’s written for. ASHP’s is built for a P&T committee, FDA’s for manufacturers. Neither one tells you what to do about one patient, one prescription, and one pharmacy that got a partial shipment Tuesday with a waitlist a mile long.

Shortages have stopped being interruptions. They’re part of the job now. The prescribers who handle them well decided how they would handle them before the call came in. That outpatient gap is where we work. Appropriate medical preparation is our name for it: a licensed provider reviews the request and writes the prescription ahead of the moment a patient needs it, for a short list of common conditions. It complements primary care, it doesn’t replace it.

If your patients are asking questions you don’t have time for, send them to us at Jase.com. We’d rather help you plan for the next shortage than help your patient recover from the last one.


Sources

  1. National Drug Shortages, January 2001 to June 2026. American Society of Health-System Pharmacists, data from the University of Utah Drug Information Service. 227 active shortages as of Q2 2026, up for a third consecutive quarter, against an all-time high of 323 in the first quarter of 2024; 89 new shortages in 2025; 16% of active shortages are controlled substances; 48% of new 2026 shortages are sole-source; manufacturers reported no reason or an unknown reason for 59% of 2025 shortages. https://www.ashp.org/drug-shortages/shortage-resources/drug-shortages-statistics 
  2. Wosińska ME. Drug shortages: a guide to policy solutions. Brookings Institution, March 13, 2024. Manufacturing quality disruptions the leading cause of shortages, 46% in 2022; generic sterile injectables 63% of current shortages. https://www.brookings.edu/articles/drug-shortages-a-guide-to-policy-solutions/ 
  3. McGeeney JD, McAden E, Sertkaya A. Analysis of Drug Shortages, 2018-2023, Introduction. Data brief prepared for HHS ASPE Office of Science and Data Policy, January 8, 2025. Purchasers have limited ability to assess manufacturers’ quality systems or backup capacity and often choose drugs solely on price, rewarding companies that reach lower costs by sacrificing investment in resilient manufacturing; facilities typically run above 80% capacity, so firms cannot easily increase production during a shortage. https://aspe.hhs.gov/reports/drug-shortages-2018-2023 
  4. McGeeney JD, McAden E, Sertkaya A. Analysis of Drug Shortages, 2018-2023, Results. Median shortage duration 2.55 years overall, 1.59 years oral, 4.60 years injectable. Three years after onset, 64.6% of injectable shortages remained unresolved, against 8.1% of orals and 26.1% of topicals. https://aspe.hhs.gov/reports/drug-shortages-2018-2023 
  5. Silverman E. The number of new drug shortages in the U.S. hits lowest level in 20 years, but myriad problems remain. STAT News, January 22, 2026, reporting ASHP’s year-end 2025 data. 89 new shortages in 2025, the fewest since 2006; ADHD medications and controlled substances remain difficult to source. https://www.statnews.com/pharmalot/2026/01/22/medicines-pharma-biotech-shortages-hospitals-injectables/ 
  6. Active US drug shortages rise for third straight quarter. AJMC. 227 active shortages as of the second quarter of 2026. https://www.ajmc.com/view/active-us-drug-shortages-rise-for-third-straight-quarter
  7. FDA vs. ASHP Drug Shortages List. American Society of Health-System Pharmacists. ASHP confirms practitioner-reported shortages at the manufacturer, strength, and fill-volume level; FDA assesses shortages against nationwide supply and demand. https://www.ashp.org/-/media/assets/drug-shortages/docs/drug-shortages-fda-vs-ashp-shortage-list.pdf 
  8. Transfer of Electronic Prescriptions for Schedules II-V Controlled Substances Between Pharmacies for Initial Filling. Drug Enforcement Administration final rule, 88 Fed. Reg. 48365 (July 27, 2023), effective August 28, 2023; Docket No. DEA-637, RIN 1117-AB64. One-time transfer for initial filling at the patient’s request, communicated directly between two licensed pharmacists, prescription unaltered and in electronic form, permissible only where state law allows. https://www.federalregister.gov/documents/2023/07/27/2023-15847/transfer-of-electronic-prescriptions-for-schedules-ii-v-controlled-substances-between-pharmacies-for

 

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For Clinicians | Psychiatric Medications in a Disaster

For Clinicians | Psychiatric Medications in a Disaster

Why Stopping and Restarting Are Two Different Hazards

By Dr. Jamie Wilkey, PharmD — Director of Clinical Strategy, Jase
Medically reviewed and edited by Kristen Carpenter, PA-C

Our last article ranked a patient’s Rx medicine cabinet so you could tell a patient which of their prescriptions genuinely can’t wait and are the most important. One row on that table needed a lot more room than we gave it. Disaster planning almost always lands on insulin and blood pressure medication, and that’s not anybody’s oversight. It’s where the evacuee data pointed, so it’s where the guidance went. We went looking for mental health medications on the standard kit lists and came up empty.

So this write up is only about mental health medications. Stopping them is one hazard and restarting them is a separate one. We’re covering two specific drugs, clozapine and lithium, and one whole class, the benzodiazepines, because all three fail in a different direction when access is disrupted with the rules of thumb that hold across the category.

Clozapine: the number of days decides the dose

When a patient on clozapine has had any gap in dosing, the first thing to establish is the date of the last dose.¹ The length of the gap is what sets the restart dose. Their maintenance dose is not the default answer.

The mechanism is loss of tolerance to clozapine’s hypotensive effect.² Current labeling puts orthostatic hypotension, bradycardia, syncope and cardiac arrest among the things that can happen “when restarting patients who have had even a brief interruption in treatment,” at doses as low as 12.5 mg a day.² The same labeling names dehydration as a predisposing condition, which is the state a lot of these patients are in during a natural disaster.

US labeling sets the restart by days missed:²

  • One day missed: resume at 40% to 50% of the previous dose
  • Two days missed: resume at roughly 25% of the previous dose
  • Anything longer: restart at 12.5 mg once or twice daily, then climb back faster than a new start

Clozapine can drive down neutrophils, the white cells that fight bacterial infection, so these patients have to get regular blood draws to check the absolute neutrophil count (ANC). If that count falls far enough, an ordinary infection can turn life-threatening. A break under 30 days doesn’t change the ANC monitoring schedule. At 30 days or more, monitoring reverts to the weekly-for-six-months schedule of a new start.² A one-week outage changes the dose and leaves the bloodwork alone. Until February 2025, the Clozapine REMS made a pharmacy verify an ANC before dispensing, so the monthly refill didn’t go out without a current lab value on file, and a patient who had drifted out of monitoring hit a hard stop at the counter.³ That backstop is gone, so the extra eye on a clozapine patient has to be yours now.

Benzodiazepines: write the plan down while you still can

For any patient on a daily benzodiazepine, the contingency plan needs to be documented while they can still reach you. Labeling is really clear and tells us why: abrupt discontinuation or rapid dose reduction after continued use “may precipitate acute withdrawal reactions, which can be life-threatening,” seizures among them.⁴ The 2025 joint tapering guideline, ten societies including ASAM and the APA, says anyone past a month of use shouldn’t stop abruptly and should taper under supervision.⁵

Withdrawal symptoms start 2 to 10 days after the last dose and can run for weeks.⁶ This is exactly why it is important to have a plan ahead of time for these medications. Withdrawal in this class needs active treatment, and a disaster is when active treatment is hardest to reach.⁶ A patient in withdrawal during an evacuation is agitated, tremulous, and tachycardic, in a setting with nothing to manage it with. 

Controlled-substance prescribing follows the same federal and state rules during a declared emergency so there isn’t disaster wiggle room here. The built-in emergency provisions are narrow, and some states bar writing for a patient the provider hasn’t examined unless that rule gets waived.⁷ 

The biggest reason patients lose access to key medications like this is structural. That means no money, no services running, or no way to get there. After Katrina, that was the reason for 74% to 84% of the people who were already in mental health treatment and then cut back or stopped.⁸ So these are the patients whose plan you prioritize. Getting through a natural disaster on a stable regimen is hard enough. Doing it in withdrawal is worse, and that’s the part planning ahead can actually change.


Lithium: the risk shows up without a missed dose

The conversation for a lithium patient is particularly interesting because in a disaster it isn’t about the medication itself that we have to worry about so much. It’s more about what the patient taking lithium is exposed to: heat, fluids, salt, and what pain medication they are using.

The kidney handles lithium a lot like sodium, so sodium or volume depletion drives reabsorption up and excretion down.⁹ Serum levels climb on an unchanged dose. Dehydration, vomiting, diarrhea, fever, and a low-sodium intake all contribute. So does a week of heat with no air conditioning, which is how a power outage affects a lithium level.

Then there’s the part that comes from the medicine cabinet instead of the weather. NSAIDs and ACE inhibitors both raise lithium levels by changing how the kidney handles sodium.⁹ A patient with a sprained ankle and a bottle of ibuprofen in a house with no power has assembled a lithium problem out of ordinary decisions.

The counseling point is early toxicity: a new tremor, GI upset, feeling unsteady.⁹ Those are vauge-ish symptoms that a patient may very well shake off as just being part of living through a natural disaster and miss them as warning signs. If these warning signs manifest then that’s a call to the prescriber, not a dose the patient adjusts on their own.

Everything else on the list

Clozapine, benzodiazepines, and lithium are the high-alert three. Most of your patients are on something else and the risk on those is different. A gap produces withdrawal symptoms, and over a longer stretch relapse, rather than the acute physiologic events the first three carry.

Two things predict how hard your patients will be hit. The first is half-life, which is just how long the drug is still doing its job after the last dose. Nobody has these memorized, and looking one up takes awhile, so here they are.¹⁰

Medication

Half-life

What that buys in a gap

Fluoxetine

4 to 16 days

Weeks of cover. Effectively self-tapering.

Vortioxetine

About 2.5 days

Several days before anything is felt.

Citalopram

About 1.5 days

Two to three days of cushion.

Escitalopram

About 1.5 days

Two to three days of cushion.

Amitriptyline

5 hours to 2 days

Range is wide. Depends on the patient.

Bupropion

21 hours

About a day, stretched by the metabolites.

Mirtazapine

20 to 38 hours

A day, sometimes two.

Sertraline

26 to 31 hours

A day, sometimes two.

Paroxetine

About 24 hours

One day, then symptoms.

Venlafaxine

About 14 hours

Under a day. One missed dose registers.

Fluvoxamine

About 14 hours

Under a day.

Duloxetine

About 12 hours

Under a day. One missed dose registers.

Desvenlafaxine

About 10 hours

Under a day.

Trazodone

3 to 9 hours, biphasic

Hours.

The second is how long they’ve been on it. Someone a few weeks into an SSRI is at low risk of serious withdrawal. Someone eight years in certainly is at a much, much higher risk of withdrawal.¹¹

Half-life is a first pass, not a verdict. Sertraline’s half-life sits above paroxetine’s, and it made almost no difference: after 5 to 8 days off, withdrawal showed up in 60% of patients taking sertraline and 66% on paroxetine, against 14% on fluoxetine.¹² The table sorts the extremes reliably. In the middle it’s a rough guide.

Oral antipsychotics and mood stabilizers don’t sort this way. Their gap risk is relapse over weeks to months rather than withdrawal over days, so half-life doesn’t predict it.

Restarting is simpler here than with clozapine. Nothing has lost tolerance, so a short gap generally resumes at the prior dose. A long one doesn’t. Reinstating a drug months after stopping it can behave unpredictably, including symptoms worsening rather than settling.¹¹

One thing not to counsel: stretching the interval. Spacing doses to every other day is the intuitive way to make what’s left go further, and for most of this list it’s the wrong move. Because so many of these half-lives run under a day, every-second-day dosing swings concentrations up and down and can precipitate severe withdrawal, which is the outcome the patient was trying to avoid.¹¹ If someone is going to run short, the prescriber reduces the dose rather than widening the interval.

Two halves of preparation

We want patients protected in a disaster, and the ones on mental health medications have been left out of many disaster preparation conversations.

Appropriate medical preparation here comes in two halves. The first is clinical, and it’s the whole article above: knowing which of your patients has no buffer, knowing that the restart is a prescriber decision rather than the patient’s, and having that decision on paper before anything happens. That first half is not a quantity, and for this class it can’t be, since controlled substances like benzodiazepines have so much red tape around dispensing them.

The second half is boring, and it’s the one that gets skipped. The formal, active, updated medication list that travels with the patient. In one Japanese flood study, 48% of evacuees left their medication behind and 88% left their prescription records behind.¹³ People remember the pills more reliably than the paper, and the paper is what lets any pharmacist or any prescriber anywhere pick up the thread.

None of this replaces primary care. It’s the layer that helps prepare a patient well with your help ahead of if/when primary care isn’t reachable.

Jase Daily: extends the list, not the benzodiazepines

Jase Daily extends a stable, existing prescription up to a 12-month supply for a patient your practice has seen within the past 6 months. That covers lithium and most of the SSRIs and SNRIs above. It doesn’t cover benzodiazepines. Jase’s pharmacy doesn’t dispense controlled substances, so a benzodiazepine patient’s continuity still runs through the written plan, not a supply workaround.


Sources

  1. ACLP How To Guide: Clozapine Consultation. Academy of Consultation-Liaison Psychiatry, 2024. Directs clinicians to determine the patient’s last clozapine dose as soon as possible, and gives a re-initiation schedule that differs from US labeling: no re-titration up to 48 hours, half the previous total daily dose then 75% then full dose over three days for a 48 to 72 hour break, 12.5 mg once or twice daily from 72 hours to one week, and titration as a new patient beyond a week. http://clpsychiatry.org/wp-content/uploads/ACLP-How-To-Guide-Clozapine-2025.pdf 
  2. Clozaril (clozapine). FDA prescribing information, revised June 2025. Identical language across Clozaril, clozapine tablets, and clozapine orally disintegrating tablets. Warnings state that orthostatic hypotension, bradycardia, syncope, and cardiac arrest have occurred, and that these reactions can occur with the first dose, at doses as low as 12.5 mg per day, or when restarting patients who have had even a brief interruption in treatment; dehydration is named among predisposing conditions. Section 2.6 sets the restart at 40% to 50% of the previous dosage after one missed day, roughly 25% after two, and 12.5 mg once or twice daily for longer gaps. ANC testing continues at the previous frequency for interruptions under 30 days and reverts to the initiating-treatment schedule, weekly for months 1 through 6, at 30 days or more. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90876802-0e3a-44c9-9ff7-1754dfbe736a 
  3. Clozapine REMS has ended. National Community Pharmacists Association, 2025. The program ended effective February 24, 2025; pharmacies no longer need ANC results before dispensing, and FDA continues to recommend prescribers monitor ANC at labeled frequencies. The current labeling contains no REMS references while retaining the ANC monitoring table. https://ncpa.org/newsroom/qam/2025/03/31/clozapine-rems-has-ended 
  4. Xanax (alprazolam). FDA prescribing information, revised April 2024. Boxed Warning states that continued use may lead to clinically significant physical dependence, and that abrupt discontinuation or rapid dosage reduction after continued use may precipitate acute withdrawal reactions, which can be life-threatening; section 5.3 names seizures as an example. Dependence risk is greater above 4 mg daily and beyond 12 weeks but exists after shorter use at lower doses. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb5cf72e-3a41-41a8-9a38-80f974eca33f 
  5. Brunner E, et al. Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits. Journal of General Internal Medicine, 2025;40(12):2814-2859. Sponsored by ten organizations including ASAM, the AAFP, and the APA. Patients taking benzodiazepines longer than a month should not abruptly discontinue and should taper under clinical supervision. https://www.asam.org/quality-care/clinical-guidelines/benzodiazepine-tapering 
  6. Regina AC, Gokarakonda SB, Attia FN. Withdrawal Syndromes. StatPearls, NCBI Bookshelf. Benzodiazepine withdrawal develops 2 to 10 days after discontinuation and can last weeks; seizures are named among the physical signs; benzodiazepine and barbiturate withdrawal are described as potentially life-threatening and requiring aggressive management. https://www.ncbi.nlm.nih.gov/books/NBK459239/ 
  7. Rutkow L, et al. Prescribing authority during emergencies: challenges for mental health care providers. Journal of Legal Medicine, 2011. Providers must follow the federal and state laws regulating prescribing during an emergency, the emergency provisions in those laws are limited, and some states do not permit prescribing for a patient the provider has not examined unless that provision is waived during a declared emergency. https://pmc.ncbi.nlm.nih.gov/articles/PMC3229266/ 
  8. Wang PS, et al. Disruption of existing mental health treatments and failure to initiate new treatments after Hurricane Katrina. American Journal of Psychiatry, 2008;165(1):34-41. Among survivors with a pre-hurricane mental disorder, 12.7% terminated and 10.2% reduced treatment, 22.9% combined. Barriers involving enabling factors, meaning financial barriers and unavailability of services plus transportation problems outside the New Orleans metro subsample, were the most commonly reported reasons for reducing or terminating treatment, at 84.0% and 74.0% across the two subsamples. https://pmc.ncbi.nlm.nih.gov/articles/PMC2248271/ 
  9. Slubicki M, et al. Lithium Toxicity. StatPearls, NCBI Bookshelf. Because the kidney handles lithium similarly to sodium, sodium or volume depletion increases renal lithium reabsorption and decreases excretion; precipitants include dehydration, vomiting, diarrhea, fever, and low-sodium diets. NSAIDs and ACE inhibitors alter renal hemodynamics or sodium handling, increasing reabsorption or reducing clearance. https://www.ncbi.nlm.nih.gov/books/NBK499992/ 
  10. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Australian Prescriber, 2016;39(3):76-83, which tabulates elimination half-lives: fluoxetine 4 to 16 days including norfluoxetine, vortioxetine 2.4 to 2.8 days, citalopram and escitalopram 1.5 days, sertraline 1.1 to 1.3 days, paroxetine 1.0 day, mirtazapine 0.8 to 1.6 days, amitriptyline 0.2 to 1.9 days, venlafaxine 0.6 days including desvenlafaxine, fluvoxamine 0.6 days, duloxetine 0.5 days, desvenlafaxine 0.4 days. https://pmc.ncbi.nlm.nih.gov/articles/PMC4919171/ Bupropion is not in that table: 21 hours, with erythrohydrobupropion about 33 and threohydrobupropion about 37 hours, from Wellbutrin XL prescribing information, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21 Trazodone is biphasic, 3 to 6 hours initial and 5 to 9 hours terminal, from Cuomo A, et al., A narrative review on trazodone as a multimodal and multifunctional antidepressant, Annals of General Psychiatry, 2026;25:32, https://pmc.ncbi.nlm.nih.gov/articles/PMC13112903/ 
  11. Therapeutics Letter 157: How to stop antidepressants. Therapeutics Initiative, University of British Columbia, 2025. Because the elimination half-life of many antidepressants is under a day, every-second-day dosing can produce wide fluctuations in drug concentrations and precipitate severe withdrawal effects. Patients on an antidepressant for only several weeks are at low risk of serious withdrawal compared with those with years of exposure, and resuming a withdrawn drug at a low dose months after stopping can have unpredictable effects including paradoxical worsening. https://www.ncbi.nlm.nih.gov/books/NBK618767/ The alternate-day modelling it draws on is O’Neill JR, et al., Alternate-day dosing to taper antidepressants risks severe withdrawal effects: an in silico analysis, Journal of Affective Disorders, 2026;392:120084, https://pubmed.ncbi.nlm.nih.gov/40848773/ 
  12. Therapeutics Letter 156: Antidepressant withdrawal syndrome, update. Therapeutics Initiative, University of British Columbia, 2025. After 5 to 8 days of discontinuation, withdrawal occurred in 14% of patients taking fluoxetine against 60% taking sertraline and 66% taking paroxetine. Paroxetine, duloxetine, and venlafaxine/desvenlafaxine are disproportionately represented in WHO withdrawal reporting. https://www.ncbi.nlm.nih.gov/books/NBK618768/ 
  13. Ochi S, et al. Disaster-Driven Evacuation and Medication Loss: a Systematic Literature Review. PLoS Currents Disasters, 2014. Seventy articles covering 27 events across 9 countries. Following Japan floods, 48% of evacuees left their medication behind and 88% left their prescription records behind. The 5.7x prepared-emergency-pack finding also comes from a single Japanese flood study inside this review rather than pooled across its 27 events. https://pmc.ncbi.nlm.nih.gov/articles/PMC4169391/ 

 

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Pink Eye: When You Actually Need Antibiotic Eye Drops

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For Clinicians | Which Medications Can’t Be Missed

For Clinicians | Which Medications Can’t Be Missed

How to Help Patients Rank their Medication List Before a Disruption

By Dr. Jamie Wilkey, PharmD — Director of Clinical Strategy, Jase
Medically reviewed and edited by Kristen Carpenter, PA-C

September is National Preparedness Month and that’s a big deal for us over here at Jase. When it comes to medications, your patients get the same advice they get every year: keep some extra medication on hand. But between all the prescription medications they take and the OTC products and supplements, that one line of advice quickly grows confusing and unmanageable. Nobody has ever published a ranking of which medications matter most, so patients sort it themselves.

Why there isn’t a ranking

One team went through 186 academic articles and 252 web pages of preparedness guidance for chronically ill patients, spanning cancer, cardiovascular disease, diabetes, chronic respiratory disease, and kidney disease. Recommended amounts on hand for the medications that treat these conditions ran anywhere from having a cushion of 3 days to a full month depending on which source you opened. Most of the recommendations traced back to expert opinion rather than evidence. None of it answers which medications actually tolerate an interruption. The review catalogues how much to have and never asks which one matters most.¹

To make matters more opaque, the literature it covered ends in 2014. The gap is still open today. So when a patient asks us how much to keep on hand, we don’t have anything more than generalities to give them.

How to rank a list

Here’s the 4 questions we use: 

  1. How sick does this patient get without this drug?
  2. How fast does that happen?
  3. How likely is this one to be short when everyone needs it?
  4. Can this particular patient actually get to a pharmacy in a bad week? 

Run a list through those and the order falls out. It’s not always what the patient expects. The table below answers the first two for the most common classes. Those are drug properties. The last two are yours, because only you know this patient.

Class

Clock

What goes wrong

What to tell them

Levothyroxine

Weeks

Seven-day half-life, so the pool drains slowly and most patients feel nothing for days.²

Put it at the bottom. Don’t spend the worry here.

Antihypertensives, the forgiving ones (ACE inhibitors, ARBs, amlodipine)

Days

Pressure drifts back toward baseline over roughly a week. Nothing rebounds.³

Resume when they can. Never double up to catch up.

Antihypertensives, the rebound ones (clonidine, beta-blockers)

Fast, and stopping is what starts it

Stopping is the event. Clonidine cessation can drive pressure past where it started, and concurrent beta-blockade makes it worse.4

Call before the last dose. This is never the one they stretch. 

Inhaled controller and rescue (asthma, COPD)

Splits by disease

In asthma, losing the controller invites an exacerbation. In COPD, withdrawal didn’t change exacerbation risk in a large trial, though lung function fell.⁵

The rescue inhaler travels with them either way.

Oral diabetes medications

Days, with one inversion

Sulfonylureas push insulin whether or not the patient ate. Skipped meals show up in most severe hypoglycemia admissions, though comorbidity drives it more than fasting alone.⁶

If food is short, the sulfonylurea is the conversation.

Proton pump inhibitors

About two weeks

Rebound acid hypersecretion after a long course. Symptoms arrive well after the last dose, then fade.⁷

Warn them that a rebound is coming and that it passes.

Insulin

Hours, and the shortest clock here

Pump therapy uses no long-acting insulin, so there’s no depot underneath it. When delivery stops, nothing is holding the floor.8

Every pump patient needs a written pen-and-syringe fallback. Check ketones if delivery stops more than an hour.

Anticoagulants (DOACs, warfarin)

Hours for DOACs, days for warfarin

DOAC half-lives run about 5 to 17 hours, so protection falls off fast. Warfarin drifts down slowly. Patients assume the reverse.9

Never double a warfarin dose after a miss.

Antiseizure medications

Days to weeks

Sustained nonadherence tracks with worse seizure control and higher mortality.¹⁰ Occasional missed doses did not acutely raise seizure risk in drug-resistant epilepsy. 11

Mid-list, not top. Consistency matters more than any single dose.

Chronic corticosteroids

Speeds up under stress

Anyone on steroids long enough to be suppressed needs more under physiologic stress, not less. A disaster is physiologic stress.¹²

Never the one to skip. Sick days need more, not less.

Psychiatric medications (antidepressants, antipsychotics, lithium, benzodiazepines)

Varies, and the clock isn’t the point

Stopping is one hazard. Restarting at the previous dose is a separate one. Part 2 of this series is all about mental health medications in a disaster

Both stopping and restarting need a plan, and both plans come from the prescriber. 

Three exceptions

The table above is great for a quick scan. Steroids, clonidine and seizure meds need more context than the table can hold.

Ask every patient on long-term steroids what they do when they get sick. If they don’t have an answer, that’s your time to shine in educating them. Physiologic stress raises the requirement, so the sick-day rule is to double the oral dose at a fever above 100.4F and triple it above 102.2F.12 Omission during stress is what precipitates adrenal crisis. A patient rationing their bottle is under stress and cutting the dose at the same time. Something to watch for sure.

Check whether your clonidine patients are also on a beta-blocker. Stopping clonidine suddenly can push blood pressure higher than it was before treatment, and being on a beta-blocker too makes that worse.4 That’s why an elective taper stops the beta-blocker several days first. Patients on both would need top priority attention if access to those medications were disrupted.

And now for epilepsy. Sustained nonadherence tracks with worse seizure control and higher mortality.¹⁰  But a prospective study published this year in drug-resistant epilepsy found that occasional missed doses did not acutely raise seizure risk.11 So they sit in the middle of the ranking, not at the top. A missed dose is not the emergency. Multiple missed doses are. 

You intuitively know which of these goes first. The patient doesn’t, not off the top of their head. So the next time their list is in front of you, help them sort it into what’s critical and what has some flexibility.

Where we sit, and what to take away

This is where Jase specializes: the undefined middle of appropriate medical preparation. We help patients get ahead of a disruption before it throws off a critical regimen, with a licensed provider reviewing every request. Disasters hit chronic conditions unevenly, and we help sort out what comes first. A complement to primary care, never a replacement for it.

The ranking is the thing to walk away with, and it’s an order rather than an amount. Every list has one drug that is most critical, and most patients aren’t clear exactly what that one is.

And now before you go you should know we still have one class that is so important that it needs its own article: psychiatric medications. Stopping them is one hazard and restarting them is another. So our next article will be a deep dive on mental health medications in a disaster.


Sources

  1. Tomio J, Sato H. Emergency and disaster preparedness for chronically ill patients: a review of recommendations. Open Access Emergency Medicine, 2014. 186 academic articles and 252 web pages screened; recommended supply ranged from 3 days to 1 month; the authors state that most of the recommendations have not been validated scientifically and that a large number rest on anecdotal evidence or expert opinion. https://pmc.ncbi.nlm.nih.gov/articles/PMC4753992/
  2. Administration and Pharmacokinetics of Levothyroxine, in 70 Years of Levothyroxine. NCBI Bookshelf. Elimination half-life averages roughly 6 to 7 days in euthyroid adults and about 7.5 days in treated hypothyroid patients, which is what supports once-daily dosing. https://www.ncbi.nlm.nih.gov/books/NBK585644/
  3. Amlodipine besylate (NORVASC). FDA prescribing information via DailyMed. Terminal elimination half-life of about 30 to 50 hours, from which a return toward baseline over several days follows. The label separately notes that amlodipine gives no protection against the dangers of abrupt beta-blocker withdrawal, which is the distinction this row turns on. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b00570ff-4081-4514-b45b-eb6f753450f5
  4. Clonidine. StatPearls, NCBI Bookshelf: abrupt discontinuation may result in rebound hypertension, the risk is higher with concurrent beta-blockade through unopposed alpha-adrenergic activity, and beta-blockers are withdrawn several days before tapering clonidine. https://www.ncbi.nlm.nih.gov/books/NBK459124/ Catapres (clonidine hydrochloride) FDA label: sudden cessation has produced nervousness, agitation, headache and tremor with a rapid rise in blood pressure and elevated plasma catecholamines, and rare instances of hypertensive encephalopathy, cerebrovascular accident and death have been reported after withdrawal. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017407s037lbl.pdf
  5. Asthma: Rank MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. Journal of Allergy and Clinical Immunology, 2013. Patients with well-controlled asthma who stop regular low-dose inhaled corticosteroids have increased exacerbation risk compared with those who continue. https://pubmed.ncbi.nlm.nih.gov/23321206/ COPD: Magnussen H, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. New England Journal of Medicine, 2014;371(14):1285-1294. 2,485 patients with a history of COPD exacerbation on triple therapy; stepwise fluticasone withdrawal over 12 weeks was noninferior for moderate or severe exacerbations, with a greater decline in lung function during the final withdrawal step. https://pubmed.ncbi.nlm.nih.gov/25196117/
  6. Burge MR, Schmitz-Fiorentino K, Fischette C, Qualls CR, Schade DS. A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus. JAMA, 1998. No hypoglycemia occurred across 156 fasting studies in elderly patients receiving maximum sulfonylurea doses. The retrospective literature reaches the opposite conclusion, with omission of one or more meals implicated in 80% of severe drug-induced hypoglycemia admissions; risk concentrates in renal or hepatic impairment, alcohol use, and polypharmacy rather than in fasting alone. https://jamanetwork.com/journals/jama/fullarticle/1150338
  7. Reimer C, Sondergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology, 2009;137(1):80-87. Randomized double-blind placebo-controlled trial in 120 healthy volunteers given 8 weeks of esomeprazole 40 mg followed by 4 weeks of placebo; clinically relevant heartburn, acid regurgitation, and dyspepsia appeared after withdrawal and persisted at least 2 weeks. Conducted in healthy volunteers, not chronic PPI patients. https://pubmed.ncbi.nlm.nih.gov/19362552/
  8. Ketones and Insulin Pumps. UCSF Diabetes Teaching Center. Pump therapy carries higher ketone risk because long-acting insulins are not used and rapid-acting insulin is delivered in very small amounts; check glucose and ketones if basal delivery is interrupted for more than an hour. https://diabetesteachingcenter.ucsf.edu/content/ketones-and-insulin-pumps
  9. Ferri N, Colombo E, Tenconi M, Baldessin L, Corsini A. Drug-Drug Interactions of Direct Oral Anticoagulants (DOACs): From Pharmacological to Clinical Practice. Pharmaceutics, 2022;14(6):1120. Elimination half-lives: rivaroxaban 5 to 9 hours in healthy adults, edoxaban 8 to 11 hours, apixaban 8 to 15 hours, dabigatran 12 to 17 hours. https://pmc.ncbi.nlm.nih.gov/articles/PMC9229376/
  10. Faught E, et al. Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM Study. Neurology, 2008. Medicaid claims analysis of 33,658 adults with epilepsy across 388,564 treated quarters, 26% of them nonadherent; nonadherence was associated with more than a threefold increase in mortality, hazard ratio 3.32 (95% CI 3.11 to 3.54). https://pubmed.ncbi.nlm.nih.gov/18565827/
  11. Goldenholz DM, et al. Does Missing Medication Acutely Change Seizure Risk? A Prospective Study. Annals of Neurology, 2026. Prospective community-based cohort of 27 adults with drug-resistant epilepsy, defined as three or more seizures per month, followed 10 months each across 7,853 person-days with 93% average adherence; occasional missed doses did not measurably raise immediate seizure risk, while prior seizure history did predict future seizures. https://pmc.ncbi.nlm.nih.gov/articles/PMC12782288/
  12. Adrenal Crisis. StatPearls, NCBI Bookshelf. Sick day rules: doubling the oral corticosteroid dose for fever exceeding 100.4°F (38°C) and tripling it for fever exceeding 102.2°F (39°C). https://www.ncbi.nlm.nih.gov/books/NBK499968/

 

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Pink Eye: When You Actually Need Antibiotic Eye Drops

Pink Eye: When You Actually Need Antibiotic Eye Drops

Pink Eye: When You Actually Need Antibiotic Eye Drops By the Jase Medical Team It’s Monday morning, and your child wakes up with one eye crusted shut. You clean it up, get everyone out the door, and hope for the best. By 9:15, the school calls. Your child has pink...

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Controlled Substances in a Disaster

Controlled Substances in a Disaster: Why the Schedule on Your Prescription Changes Everything By the Jase Medical Team ou evacuated with four days of medication in your bag. Now you're two states from home, the pharmacy holding your prescription is closed, and you're...

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For Clinicians | Purulent vs. Nonpurulent Cellulitis

For Clinicians | Purulent vs. Nonpurulent Cellulitis

What an Antibiotic Can’t Do for a Wound

By Dr. Jamie Wilkey, PharmD — Director of Clinical Strategy, Jase
Medically reviewed and edited by Kristen Carpenter, PA-C

Most of what goes wrong with a wound isn’t fixed by an antibiotic. Your patients are working that out on day three, alone, with something left over in the closet. Today we’re covering antibiotic prescribing basics, the things a pill can’t touch, and the presentations that get seen rather than treated.

Purulent and nonpurulent: two kinds of wound trouble

Almost everything that goes wrong with a wound is one of two problems, and they behave nothing alike.

Purulent is a pocket. Pus collects in one place, the body walls it off, and pressure builds inside. You can feel it: a tender lump that gets firmer, then squishy in the middle. Abscess, furuncle, carbuncle, all the same problem at different sizes. It doesn’t spread so much as it grows and tightens, and it keeps going until something opens it, either a blade or the skin giving way on its own. 

Nonpurulent is a spread. There’s no pocket to find. Infection moves outward through the tissue, so the red edge sits somewhere different tomorrow than it did today. That’s cellulitis, and the border is the thing to watch. 

An antibiotic travels in the blood, and blood is the one thing that doesn’t reach the middle of a walled-off pocket. Therefore, a pocket has to get opened for treatment. A spread gets a drug to heal because that drug will actually reach the infection site. Draining an abscess is the treatment, not the prep work before the real treatment.

Which drug does which job

Purulent, once it’s drained, often needs nothing at all. That surprises people, so here it is straight from the guideline: for a simple abscess that’s been opened, systemic antibiotics are unnecessary, even when the organism is MRSA.¹ The drainage did the work. A drug gets added when the patient meets SIRS criteria or has genuinely impaired host defenses, not because a scary name came back on the culture.¹

Nonpurulent is the one that actually needs a drug. There’s nothing to open, so the treatment is systemic and it aims at strep: penicillin VK or cephalexin.¹ Cephalexin is 500 mg every six hours. The twice-a-day scripts that come through for a red leg are underdosed for it. The article reviewer, Kristen, has a family member who is an infectious disease doctor and she always says so many people underdose cephalexin and that is the reason it fails, not because it was “resistant”.

So of the two problems in front of you, the pill is the primary treatment in exactly one. The other one needs a blade.

When MRSA actually enters the picture

Pus means staph, and staph in the community is frequently MRSA. No pus usually means strep, and strep is never MRSA. So MRSA lives in the abscess, and the abscess, once it’s drained, usually needs no antibiotic at all.

This leaves our MRSA treatment reflex pointed at the wrong wound. The red leg with no pocket is where doxycycline gets added in practice, and it’s the presentation where MRSA is least likely to be.

The pair itself isn’t wrong. Cephalexin covers strep and misses MRSA. Doxycycline and trimethoprim-sulfamethoxazole cover MRSA and are shakier on strep. When you truly need both, IDSA’s oral answer is clindamycin alone or a beta-lactam paired with one of those two.¹ A real regimen, but used inappropriately at times when only strep needed covering.

So somebody ran that trial. Five hundred patients with uncomplicated cellulitis, cephalexin plus Bactrim against cephalexin plus placebo. Cure rates came back two points apart, with cephalexin alone on the higher end.² Cephalexin plus Bactrim isn’t a better treatment than cephalexin alone, and the trial’s own authors couldn’t rule out a small benefit they’d want tested again.

Nobody gets to say cephalexin alone wins. But it isn’t the no-brainer it feels like either, and that’s enough to make the next red leg worth a “why are we still doing this?”

MRSA coverage (Bactrim or doxycycline by mouth) belongs in two places: a drained abscess in someone with systemic signs or impaired host defenses, and cellulitis where there’s a real reason to suspect it, like penetrating trauma, known MRSA, or injection drug use.¹

What a pill can’t touch

Tetanus is the big one here. The ten-year vaccine interval is for clean, minor wounds. For a dirty one, and that means a puncture, a crush, a burn, or anything carrying soil or saliva, the interval is five years.³ Somebody eight years out from their last booster who steps on a nail in the garden is due, even though the ten-year rule will tell them they’re fine. Either Td or Tdap works for wound prophylaxis.³

Diabetes and peripheral vascular disease change the math, in two different ways that get collapsed into one. Poor perfusion means the wound closes slowly and infection is harder to clear. Neuropathy is the other problem, and it sits upstream of all of it: an injury goes unnoticed because the pain that normally makes a person look never arrives. By the time the wound is seen, it’s older than the patient’s story suggests.⁴

Then the one that isn’t an antibiotic decision at all. Pain out of proportion to what the skin shows, a border moving while you watch it, systemic toxicity, crepitus or bullae. That’s a necrotizing infection until proven otherwise, and IDSA’s line is prompt surgical consultation:¹ a surgeon tonight rather than a prescription and a recheck in the morning.

The guideline is twelve years old

The guideline I keep quoting is from 2014, and it’s still the current US document. Two randomized trials since then complicate what I told you about drained abscesses. Talan found Bactrim after drainage raised cure from roughly 74% to 80%.⁵ Daum found the same direction in abscesses under 5 cm.⁶ Both landed within three years of the guideline, and the guideline still says what it said.

None of it answers what the patient is actually asking, which is what to do about their own leg on day three.

The missing middle

Right now this is all or none. Either the patient gets to you and you look at the leg, or they’re navigating this on their own (offgrid, trapped by a natural disaster, or in a foreign country to name a few scenarios). Nothing sits in between, where somebody has already told them which version of this kind of infection needs a healthcare professional’s eyes on it.

That in-between is our work, and it has a name: appropriate medical preparation. It isn’t a replacement for primary care, and this article is the argument for why. Half of what we’ve covered is something only a clinician can do.

We’re medical doctors, PAs, and pharmacists, and we spend our time charting the parts of this that the guidelines leave grey. If a patient is pressing you for something to keep on hand and you don’t have the bandwidth for it, send them to us at Jase.com. A licensed provider reviews the request and writes the prescription, and we’ll keep publishing where we draw the lines.

The bottom line

Most of what goes wrong with a wound isn’t fixed by an antibiotic. Some of it gets opened, some of it is a tetanus shot, some of it needs a surgeon tonight, and a good share of it was never an infection at all.

When specialists re-examined patients who’d been diagnosed with cellulitis, 41% had something else, usually stasis dermatitis, eczema, or lymphedema.⁷ That’s trained clinicians, examining the patient in person, getting it wrong four times out of ten. Your patient, looking at their own leg and typing symptoms into a phone, is not going to do better.


Sources

  1. Stevens DL, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52. https://academic.oup.com/cid/article/59/2/e10/2895845 
  2. Moran GJ, Krishnadasan A, Mower WR, et al. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial. JAMA. 2017;317(20):2088-2096. https://pmc.ncbi.nlm.nih.gov/articles/PMC5815038/ 
  3. Centers for Disease Control and Prevention. Tetanus. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book), chapter 21. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-21-tetanus.html 
  4. Senneville É, Albalawi Z, van Asten SA, et al. IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023). Clin Infect Dis. 2023. https://pubmed.ncbi.nlm.nih.gov/37779323/ 
  5. Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-832. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851110/ 
  6. Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555. https://pmc.ncbi.nlm.nih.gov/articles/PMC6886470/ 
  7. Nightingale R, et al. Misdiagnosis of Uncomplicated Cellulitis: a Systematic Review and Meta-analysis. J Gen Intern Med. 2023;38(10):2396-2404. https://link.springer.com/article/10.1007/s11606-023-08229-w 

 

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