question: what causes the reduce in potency of medicines like ibuprofen after they expire?
comment: Many medicines are comprised of both active and inactive ingredients. The inactive ingredients serve as stabilizers, fillers, absorption enablers, etc. Over time, and with exposure to air and potentially other contaminants, there ingredients begin to break down, degrade, and otherwise change the way the body interacts with the active ingredient. In addition, various contaminants, oils, dirt, etc may be introduced into the container as the user invariably dumps out several and puts the remainder back. These too can potentially allow for bacterial grown and weakening/changing of potency.
passages: The American Medical Association (AMA) issued a report and statement on Pharmaceutical Expiration Dates. The Harvard Medical School Family Health Guide notes that, with rare exceptions, "it's true the effectiveness of a drug may decrease over time, but much of the original potency still remains even a decade after the expiration date".
   The expiration date of pharmaceuticals specifies the date the manufacturer guarantees the full potency and safety of a drug. Most medications continue to be effective and safe for a time after the expiration date. A rare exception is a case of renal tubular acidosis purportedly caused by expired tetracycline. A study conducted by the U.S. Food and Drug Administration covered over 100 drugs, prescription and over-the-counter. The study showed that about 90% of them were safe and effective as long as 15 years past their expiration dates. Joel Davis, a former FDA expiration-date compliance chief, said that with a handful of exceptions - notably nitroglycerin, insulin and some liquid antibiotics - most expired drugs are probably effective.
   The expiration date printed on drug packaging will differ from the true expiration date of the drug. Before the true expiration of a drug, its active ingredient will retain its potency. Also before expiration, no components of the drug will degrade to become harmful. Since products continually change over time, the characteristics of any drug are not unchanging but instead estimated with assay measurements to be within the specification required by the government regulator where the drug is sold. As a general estimate, a drug becomes unfit for use when 10% of the active ingredient is degraded.
   To reduce the cost to the military of maintaining stockpiles of certain pharmaceuticals, the United States Department of Defense and the Food and Drug Administration operate a joint initiative known as the Shelf Life Protection Program (SLEP), which evaluates the long-term effectiveness of medications stockpiled by the DoD and other government agencies. Under the program, medications are tested for safety and stability for extended periods of time in controlled storage conditions. In many cases, medications tested were found to be effective for years past their printed expiry dates; a 2006 study by the Journal of Pharmaceutical Sciences found that two-thirds of 122 medications tested through SLEP remained effective for an average of at least four additional years. In 2016, the DoD reported that the program had helped save the department $2.1 billion on replacing stockpiled medications.
   The expiration date of pharmaceuticals specifies the date the manufacturer guarantees the full potency and safety of a drug. Most medications continue to be effective and safe for a time after the expiration date. A rare exception is a case of renal tubular acidosis purportedly caused by expired tetracycline. A study conducted by the U.S. Food and Drug Administration covered over 100 drugs, prescription and over-the-counter. The study showed that about 90% of them were safe and effective as long as 15 years past their expiration dates. Joel Davis, a former FDA expiration-date compliance chief, said that with a handful of exceptions - notably nitroglycerin, insulin and some liquid antibiotics - most expired drugs are probably effective.
   Shelf Life Extension Program
  
  The Shelf Life Extension Program (SLEP) is a joint program of the United States Department of Defense and the Food and Drug Administration that aims to reduce the cost to the military of maintaining stockpiles of certain pharmaceuticals by researching the expiration of drugs. It tests medications for safety and stability for extended periods of time in controlled storage conditions. In many cases, medications remain effective for years after their printed expiry dates.
  
  Section::::External links.
  
  BULLET::::- SLEP - The DOD/FDA Shelf Life Extension Program
  
  BULLET::::- SLEP information paper - (Archived Copy)
  
  BULLET::::- Other studies
   Several tools exist to help physicians decide when to deprescribe and what medications can be added to a pharmaceutical regimen. The Beers Criteria and the STOPP/START criteria help identify medications that have the highest risk of adverse drug events (ADE) and drug-drug interactions. The Medication appropriateness tool for comorbid health conditions during dementia (MATCH-D) is the only tool available specifically for people with dementia, and also cautions against polypharmacy and complex medication regimens.
   Drug expiration
  
  Drug expiration is the date after which a drug might not be suitable for use as manufactured. Consumers can determine the shelf life for a drug by checking its pharmaceutical packaging for an expiration date.
   Some consumers can face the difficult position of being unable to afford their medication, and choosing between using expired medication or forgoing medication. An epipen is an example of an expensive medication which someone might consider using after expiration because of inability to purchase newer medication. Some common drugs which authorities say are always unsafe if expired include nitroglycerin, insulin, and liquid antibiotics.
   BULLET::::- Following single or multiple IV infusion, the peak plasma concentrations (C) of eteplirsen occurred near the end of infusion and plasma concentration-time profiles of eteplirsen were generally similar and showed multi-phasic decline; the majority of drug elimination occurred within 24 hours.
  
  BULLET::::- Plasma protein binding of eteplirsen in human is relatively low, ranging 6.1~16.5% and is independent of concentration studied.
  
  Section::::Nature and sequence of oligo and target.
  
  Eteplirsen is a morpholino phosphorodiamidate antisense oligomer.
  
  CTCCAACATCAAGGAAGATGGCATTTCTAG (sequence source: US FDA ETEPLIRSEN BRIEFING DOCUMENT NDA 206488),
  
  30-mer,
  
  20% G,
  
  43% CG,
  
  Predicted Tm: 88.9 °C at 10 µM oligo.
  
  Oligo complement
  
  CTAGAAATGCCATCTTCCTTGATGTTGGAG
   If the nadir ANC  500/μL for 10 days or more, or if the nadir platelet count at every time falls below 25,000/μL, then the doses of etoposide, doxorubicin and cyclophosphamide are reduced by 20% below the doses used in the previous cycle, but doxorubicin and etoposide should not be reduced below the initial dose (dose in first course).
   The chemical half-life of naloxone is such that injection and nasal forms have been marketed with 24-month and 18-month shelf-lives, respectively. A 2018 study noted that the nasal and injection forms presented as chemically stable to 36- and 28-months, respectively, which prompted an as yet incomplete five year stability study to be initiated. This suggests that expired caches of material in community and healthcare settings may still be efficacious substantially beyond their labeled expiration dates.
  
  Section::::History.
   Section::::Availability.:Oxymorphone oral dosage forms.
  
  Oxymorphone comes in a variety of doses.
  
  Section::::Special populations.
  
  Patients already suffering from debilitation are at a much higher risk of respiratory depression. Nonopioid analgesics should be considered in this population.
  
  Elderly patients are much more sensitive to adverse effects, such as falls, cognitive impairment and constipation, and should be monitored for such. Decreased renal function associated with aging leads to decreased clearance of the drug, resulting in narrow therapeutic windows and increasing the danger of overdose. If oxymorphone is absolutely indicated, smaller initial doses should be started for this population.
   The patient continues taking warfarin with aspirin for 45 days post implantation at which point in time they return for a transesophageal echocardiography to judge completeness of the closure and the presence of blood clots. If the seal is complete (no gaps around the device larger than 5mm with communication to the appendage), then the patient can stop taking warfarin and start clopidogrel and aspirin for 6 months after implant. At 6 months post implantation, it is recommended for the patient to continue taking aspirin indefinitely. In the PREVAIL clinical trial, 92% of patients stopped taking warfarin after 45 days and 99% discontinued warfarin at 1 year.
   Benoxaprofen has a rather long half life in man (t= 20-30 h), undergoes biliary excretion and enterohepatic circulation and is also known to have a slow plasma clearance (CL p=4.5 ml/min). The half life may be further increased in elderly patients (80 years of age) and in patients which already have an renal impairment increasing to figures as high as 148 hours.
   Section::::Overview.
  
  Section::::Overview.:Normal QT interval.
   Before choosing an expiration date to print the manufacturer must first decide a true expiration date. After a manufacturer has decided what true expiration date it has set, then it will decide another date to make public and advertise on the packaging of the drug. The printed expiration date will always be sooner than the true expiration date, because the drug should always be effective and safe before the labeled expiration date if kept properly.
  
  Section::::Options for expired drugs.
  
  Section::::Options for expired drugs.:Disposal.
   For people with a life limiting condition such as a dementia, it is important to consider when to discontinue medications used to prevent future serious events. The Medication Appropriateness Tool for Comorbid Health conditions during Dementia (MATCH-D) provides guidance for clinicians and consumers on how to manage medications..
  
  Section::::Effects.
  
  Drug discontinuation may cause rebound effects (return of the symptoms the drug relieved, and that, to a degree stronger than they were before treatment first began) and withdrawal syndromes (symptoms caused by the discontinuation by the drug itself).
   A study conducted by the U.S. Food and Drug Administration covered over 100 drugs, prescription and over-the-counter. The results showed that about 85% of them were safe and effective as far as 15 years past their expiration date. Joel Davis, a former FDA expiration-date compliance chief, said that with a handful of exceptions—notably nitroglycerin, insulin, some liquid antibiotics; outdated tetracyclines can cause Fanconi syndrome—most expired drugs are probably effective.
   Section::::Incidence.
   Pfizer's main patent for Lyrica, for seizure disorders, in the UK expired in 2013. In November 2018 the Supreme Court of the United Kingdom ruled that Pfizer's second patent on the drug, for treatment of pain, was invalid because there was a lack of evidence for the conditions it covered – central and peripheral neuropathic pain. From October 2015 GPs were forced to change patients from generic pregabalin to branded until the second patent ran out in July 2017. This cost the NHS £502 million.
  
  Section::::External links.
  
  BULLET::::- U.S. prescribing information
  
  BULLET::::- Pregabalin Material Safety Data Sheet
   Epileptic seizures are the most important adverse effect of bupropion. A high incidence of seizures was responsible for the temporary withdrawal of the drug from the market between 1986 and 1989. The risk of seizure is strongly dose-dependent, but also dependent on the preparation. The sustained-release preparation is associated with a seizure incidence of 0.1% at daily dosages of less than 300 mg of bupropion and 0.4% at 300–400 mg. The immediate release preparation is associated with a seizure incidence of 0.4% for dosages below 450 mg; the incidence climbs to 5% for dosages between 450–600 mg per day. For comparison, the incidence of unprovoked seizure in the general population is 0.07 to 0.09%, and the risk of seizure for a variety of other antidepressants is generally between 0.1 and 1.5% at recommended dosage levels. Clinical depression itself has been reported to increase the occurrence of seizures, and a study examining FDA clinical trial data has suggested that in most cases, low to moderate doses of antidepressants may not actually increase seizure risk at all. However, this study also found that bupropion and clomipramine were unique among antidepressants in that they were associated with increased incidence of seizures.
   When discontinuing treatment with duloxetine, the manufacturer recommends a gradual reduction in the dose, rather than abrupt cessation, whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
   Although it is difficult to predict which individuals will be affected from drug-induced long QT syndrome, there are general risk factors that can be associated with the use of certain medications.
   The infusion rate is normally initiated at 1.25 ng/kg/min for new patients, but may be reduced to 0.625 ng/kg/min if the normal rate provokes unwanted side effects in the patient. The infusion rate of treprostinil should be increased no more than 1.25 ng/kg/min per week for the first month, then 2.5 ng/kg/min per week for the remaining duration of infusion. The infusion rate should ideally be high enough to improve symptoms of pulmonary hypertension, while minimizing unpleasant side effects (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction). Dosage adjustments may be undertaken more often if tolerated. There is little experience with doses 40 ng/kg/min. Abrupt cessation of infusion should be avoided. Restarting a Remodulin infusion within a few hours after an interruption can be done using the same dose rate. Interruptions for longer periods may require the dose of Remodulin to be re-titrated.
  