Tuesday, May 08, 2012

RUM 5- Cheaper Medicines and AMR

Getting cheap, if not free, medicines and vaccines is a primacy concern for many people, especially the poor. And understandably so. But people seldom realize that while drugs can heal, they can also kill -- via non-rational use of medicines (RUM) and its variants: non-rational storage, non-disposal of possibly expired or ineffective medicines. And one adverse health outcome due to non-RUM is the development of anti-microbial resistance (AMR).

Below are some discussion papers about proper use, care, storage, and disposal of medicines. One from the  World Health Organization (WHO) and three from Reiner Gloor, PHAP Executive Director, in his columns in BusinessWorld (www.bworldonline.com) last year.

1. Antimicrobial resistance -- from WHO
2. Disposing medicines -- from Reiner Gloor
3. Storing medicines
4. Ensuring patient safety

Enjoy reading.

(1) Antimicrobial resistance

Fact sheet N°194
Reviewed March 2012

Key facts

* Infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness and greater risk of death.
* About 440 000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge annually, causing at least 150 000 deaths.
* Resistance to earlier generation antimalarial medicines such as chloroquine and sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries.
* A high percentage of hospital-acquired infections are caused by highly resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).
* Inappropriate and irrational use of antimicrobial medicines provides favourable conditions for resistant microorganisms to emerge, spread and persist.

What is antimicrobial resistance?

Antimicrobial resistance (AMR) is resistance of a microorganism to an antimicrobial medicine to which it was previously sensitive. Resistant organisms (they include bacteria, viruses and some parasites) are able to withstand attack by antimicrobial medicines, such as antibiotics, antivirals, and antimalarials, so that standard treatments become ineffective and infections persist and may spread to others. AMR is a consequence of the use, particularly the misuse, of antimicrobial medicines and develops when a microorganism mutates or acquires a resistance gene.....

(2) Disposing medicines

Medicine Cabinet -- By Reiner W. Gloor
May 6, 2011

Medicines offer a promise to provide prevention, management and cure for simple to complex illnesses. Many of us find it necessary to take some personal medicines at home. But when the time comes when medicines are no longer needed, disposing them properly is important to avoid causing unnecessary harm to people, animals, food supply chain and the environment.

Proper medicine storage is as important as its proper disposal. The same applies to antibiotics, which inappropriate and irrational use lead to anti-microbial resistance (AMR).

One of the industry medical directors, Dr. Luis Abola of Bayer said that patients must not self-medicate to avoid developing AMR.

Storing leftover antibiotics even after the course of treatment is completed increases the chances of self-medication the next time around.

A number of safe methods for safe disposal of medicines were outlined by the WHO (World Health Organization) Guidelines for Safe Disposal of Unwanted Pharmaceuticals in and after Emergencies. Developed in 1999, the document stressed that the improper disposal of medicines may be hazardous if it leads to contamination of water supplies or local sources used by nearby communities or wildlife.

If medicines are not disposed properly, they may end up with scavengers, children and animals or may even be diverted to the market for resale and misuse.

In the Philippines, the proper disposal of medicines became an issue when expired products were found buried in a provincial government compound in 1999. About 26 kinds of medicines were reportedly dug up in a 10-foot-deep pit in the engineering office compound in a northern province.

Earlier, the Department of Health (DoH) and the Department of Natural Resources (DENR) produced the Health Care Waste Management Manual with the goal of minimizing health and environmental concerns associated with the disposal of unneeded medicines, among others.

With the implementation of the Clean Air Act of 1999, the use of incineration as a method in treating health care waste is no longer allowed. The DoH-DENR Manual listed alternative technologies for the proper disposal of health care wastes, one of which is the thermal process that converts the wastes into gaseous, liquid or solid forms. Another alternative is the waste immobilization process where pharmaceutical wastes are mixed with water, cement and lime to form a homogenous paste. A third method involves immobilizing the pharmaceuticals in a solid block within a plastic or steel drum.

Understanding some general guidelines on the proper disposal of medicines will help us manage any unused, unneeded and expired medicines at home with the same goal of protecting human life and the environment.

So, how do we dispose medicines at home? First, read the medication’s information leaflet for any special instructions concerning appropriate disposal. If there are no specific instructions, the US Food and Drug Administration (FDA) said that almost all medicines can be thrown away in the household trash.

However, the FDA recommends a few precautionary measures. The suggestion is to mix the medicine with undesirable substances such coffee grounds and kitty litter to make it unattractive for children, scavengers and animals. One can also place the medicine inside a sealed plastic bag or container to prevent leakage.

We must also erase all identifying information on the prescription label to make it unreadable. Doing so will reduce other people’s interest in the medicine since they would not know what it is intended for.

But must all medicines go to ordinary household trash?

The answer is no. The FDA has listed some medicines that need to be flushed down the sink or toilet. The medicines intended to be discarded this way include those that contain active ingredients such as fentanyl citrate, morphine citrate, methylphenidate, and meperidine hydrochloride among others. (To see the full list, go to http://www.fda.gov/Drugs/ResourcesForYou/Consumers)

The objective of flushing down some medicines is to minimize, if not eliminate, any accidental exposure to these substances. Fatal poisoning cases especially among young children have been reported due to the accidental intake of these medicines.

In response to environmental concerns related to flushing down medicines, the FDA said that the known risk of harm to humans from accidental exposure far outweighs any potential risk to the environment.

Then again, the US Environmental Protection Agency (EPA) stressed that patients must only flush medicines when indicated. It noted that some medicines, vitamins and other supplements flushed down may pass through wastewater treatment plants and eventually enter water sources and then go to food sources like fields. The EPA added that water treatment plants are generally not equipped to routinely remove medicines and supplements.

Cleaning our medicine cabinets to remove unused, unneeded and expired medicines may take a portion of our time but it could help save lives. Properly disposing them will not only keep people, especially children, safe but will also make known our concern for the environment.

(3) Storing medicines

Medicine Cabinet -- Reiner W. Gloor
April 29, 2011

Pharmaceutical research and development (R&D) is a long, complex and expensive process necessary to discover and produce a medicine that will help save and improve lives. The various stages of discovery and clinical trials are important to ensure the effectivity, quality and safety profile of a medicine.
But for the pharmaceutical industry, the bulk of the work does not end with a successful R&D. As soon as a medicine is approved for patient use, other processes to ensure patient safety and drug efficacy are set in motion.

As discussed in earlier columns, one is the science called pharmacovigilance which relates to the careful detection, assessment, understanding and prevention of unintentional adverse effects or medicine-related problems.

Strict adherence to global standards concerning storage and distribution of pharmaceutical products is always required throughout the distribution chain.

One of the major roles of the pharmaceutical industry is to ensure that the pharmaceutical supply chain is protected until medicines reach the patients through more than 16,000 pharmacies across the country including hospitals and drugstores in the Philippines.

Distributing and storing pharmaceutical products throughout various geographic areas can be challenging. Medicines are unlike other consumer goods, except maybe food, since they are sensitive to external forces. Therefore, their distribution is governed by strict transport, storage and disposal regulations usually issued by the manufacturers based on stability studies. The movement of pharmaceutical products begins at manufacturing plants, moves to a central warehouse, then to a regional transport and storage facility, then to the pharmacies and finally, the patients. These movements involve distributors, forwarders, wholesalers and subdistributors.

As defined by the World Health Organization (WHO), Good Distribution Practices (GDP) are part of quality assurance that ensure that the quality of a pharmaceutical product is maintained through adequate control throughout the numerous activities which occur during the distribution process.

The GDP guideline involves Good Storage Practices which ensure that the quality of pharmaceutical products is maintained through adequate control throughout storage.

The WHO specified that pharmaceutical storage locations must be designed to ensure good, orderly, and sufficient storage conditions. Compliance to the guideline would mean that storage areas must be clean, dry and maintained within temperatures recommended by manufacturers. Where special storage conditions are required on the label such as temperature and relative humidity, these should also be provided, regularly checked, monitored and recorded.

Global standards and practices on the distribution and storage of pharmaceutical products are important to ensure the integrity and quality of medicines. Drugs react to external stimulants such as heat, moisture, light and dust, among others.

In many cases, these stimulants lead only to superficial changes like discoloration. However, in other cases, the non-proper handling and storage of drugs may affect the drug’s efficacy and/or potency.

Some medicines, if subjected to external forces, do not only affect their efficacy and/or potency but may also adversely affect the patient.

As you get familiar with your medicines, you will notice that they indicate temperature guide in the product labels. In many cases, the labels indicate, "Store at temperatures not exceeding…" or "Keep in cool, dry place."

Vaccines require mandatory storage and handling procedures. It requires the so-called "cold chain" where vaccines must be stored between +2°C to +8°C from the time a vaccine is manufactured, to the time it is administered. With the special storage and handling procedures for vaccines, they must not be stored at home.

The WHO guideline added that pharmaceutical products are also stored off the floor and suitably spaced to permit cleaning and inspection.

Since storage areas need to be clean and free from accumulated waste and vermin, sanitation and pest control programs are a must. On the other hand, these measures must not pose risk of contamination of the materials and pharmaceutical products.

Radioactive materials, narcotics and other hazardous, sensitive and/or dangerous pharmaceutical products, as well as products presenting special risks of abuse, fire or explosion, are likewise stored in a dedicated area that is subject to appropriate additional safety and security measures.

The guideline also states that pharmaceutical products should be handled and stored in such a manner as to prevent contamination, mix-ups and cross-contamination.

To ensure that products are always fresh, pharmaceutical products with the nearest expiry date are distributed first. Where no expiry dates exist for the products, the First In, First Out principle should be applied.

Since many of us find it necessary to keep some medicines at home, how pharmaceutical products are being handled by the industry will help us determine how we should properly store medicines at home.

First, it is important to read the product’s label for proper guidance on the correct storage condition. Patients must always demand for the medicine information leaflet from pharmacists if they are buying in smaller quantities.

As mentioned, we should store medicines away from direct light, heat, and moisture. Keeping them near windows, in the bathrooms or near the stove may not help.

Medicines in our cabinets must also be segregated such as those currently used and those not currently used but not yet expired.

It will also be wise to store them in their original containers to avoid mix-ups and to keep product information such as batch numbers and expiration dates.

Since there have been incidents of children unintentionally swallowing medications, it is important that we keep medicines in secured cabinets out of reach of young ones.

Individuals must also be aware of signs of degradation or decomposition such as but not limited to discoloration, and melting of capsules and tablets and other solid dosage forms.

Finally, discard items which are expired or manifest signs of degradation or decomposition.

As we go on vacation, we also find it practical to bring along some of our medicines. When traveling abroad, it is best to bring the doctor’s prescription to avoid unnecessary confiscation of medicines by the customs officer. Apart from the above mentioned, we must also not leave medicines in vehicles for a long period of time. One can place medicines in a clean and sealed organizer. They may be organized according to frequency of intake.

From the R&D process, pharmacovigilance, storage and up to distribution, all measures are being taken to ensure medicine quality and safety. Handling medicines with care at home and during travels is an individual responsibility that will allow you to maximize their benefits.

(4) Ensuring patient safety from the lab to your ‘medicine cabinet’

Medicine Cabinet By -- Reiner W. Gloor
January 20, 2011

Surveillance is one of the most common terms used in law enforcement. Stories about military or police surveillance also abound in the entertainment scene with a movie about a tourist placed under close watch in Paris and Venice dominating the big screen early this year.

The term surveillance is a French word which literally means “to watch from above.” In general, it is a process of close monitoring or tight observation of persons, groups, events or behaviors. In pharmaceutical research and development, a similar kind of surveillance is crucial in ensuring patient safety each time a patient takes a medicine. This process relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem is called pharmacovigilance.

Dr. Emmanuel Arca, medical affairs manager for cardiology and patient safety of AstraZeneca, explained that pharmacovigilance and post-marketing surveillance activities are essential to monitor undetected and unlisted adverse events during the research and development process. The World Health Organization (WHO) also stated that pharmacovigilance is a vigilant assessment of the risks and benefits of medicines which applies throughout the life cycle of a medicine -- from the pre-approval stage until the time they are already approved and being used by the patients.

As explained in recent columns, pharmaceutical R&D can take an average of 10 to 15 years with costs reaching up to $800 million to $1 billion. The R&D process involves pre-clinical testing and the three phases of actual clinical trials in humans. During clinical trials, up to 5,000 volunteers from different countries are needed to establish that a drug produces the desired effects as well as note any side effects.

Continually monitoring medicines after the manufacturing stage will establish new and emerging safety and efficacy data, being exposed to a larger number of patients as compared to while it was still in development and conditions of actual use as compared to the “controlled” environment during clinical trials.

Ideally, all companies engaged in the manufacture, marketing and distribution of medicines should have a pharmacovigilance system in place, in cooperation with the local health and regulatory authorities, to ensure product quality and patient safety. Pharmacovigilance activities include monitoring and reporting of adverse events and conduct of local studies, among other related activities, that would assess the safety and tolerability of a drug among local patients.

What exactly are adverse events? When you open any box of medicine, you can’t miss the information leaflet that comes with it. This leaflet contains information on adverse events among others. But there are times when information leaflets are not given because we do not get to buy the entire box. Therefore, it is very important for patients to demand this literature from the pharmacist. Dr. Arca defined an adverse event (AE) as any undesirable medical condition that arises at a time an individual is taking a drug, whether or not it is directly due to the drug. An adverse drug reaction (ADR), on the other hand, is an adverse event that is causality related or due to the drug.

As the WHO explained, all medicines have benefits but no drug is without risk. Pharmacovigilance seeks to address this as its aims are to enhance patient care and patient safety in relation to the use of medicines -- especially with regard to the prevention of unintended harm and contribute to the assessment of the risk-benefit profile of medicines.

Majority of the ADRs can be prevented though, added the WHO. The ADRs can be due to prescription of the wrong drug or the wrong dosage of the right drug. It can also be because of an undetected medical, genetic or allergic condition that causes patient reaction.

ADR can sometimes be due to self-medication with prescription medicines or reactions with other drugs and certain foods. With these, Dr. Arca stressed that patients must always consult with a qualified health care professional for proper diagnosis and management of any disease.

ADRs can also be caused by substandard medicines with composition below the correct scientific requirements or it can be due to the use of counterfeit drugs. Pharmacovigilance is one of the essential tools in detecting counterfeit medicines. Patients who developed AEs when taking a drug should be investigated and investigation can sometimes lead to detection of counterfeit medications.

As defined by Republic Act No. 8203 also known as Special Law on Counterfeit Drugs, Section 3, counterfeit drug or medicine refers to “medicinal products with the correct ingredients but not in the amounts as provided hereunder, wrong ingredients, without active ingredients, with sufficient quantity of active ingredient, which results in the reduction of the drug’s safety, efficacy, quality, strength or purity.”

It is a drug which is deliberately and fraudulently mislabeled with respect to identity and/or source or with fake packaging, and can apply to both branded and generic products.

In many cases, fake medicines cause great harm and worse, fatalities among adults and even children. They can cause allergic reactions, heavy metal poisoning, as well as promote drug resistance to strains of diseases.

For many medicines, the pharmaceutical industry’s work is far from over even after the manufacturing stage. We are part of an industry that would continually care for the patients even after our medicines are already in your homes. While we take to heart our duty to ensure patient safety through pharmacovigilance, it is a matter that concerns us all. Health and regulatory agencies, hospitals, health care professionals, academe, industry players, patients, among others play a critical role in the success of this activity.

With this, PHAP is urging the public to be vigilant and to report if ever safety issues will arise due to exposure and intake of medication. A patient can report safety issues to the Food and Drug Administration or even to PHAP. PHAP is part of a multi-stakeholder alliance called the Safe Medicines Network (SMN) that advocates patient safety to safeguard the public against fake medicines. You may call the SMN hotline at 1-800-10-FAKEMED for any report on counterfeit drugs.

Medicine Cabinet is a column by the Pharmaceutical and Healthcare Association of the Philippines (PHAP) representing the country’s trusted providers of quality, innovative and safe medicines. It is a lead advocate of universal health care to achieve better health for Filipinos.

See also:
RUM 1: Reducing Medicine Abuse, January 25, 2012
RUM 2: SARAH, Drug Dependence, January 30, 2012
RUM 3: On Combining Drug Molecules and Alaxan FR, February 03, 2012
RUM 4: Dealing with Drug-Resistant Diseases, April 24, 2012

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