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OTC drugsBelal A Dabour & Mahmoud W Qandeel

Supervised by : Dr.Jehad H Hammad

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History

• For millennia, people used many different remedies for therapeutic and cosmetic uses.

• With the major advances in medicine and chemistry, the list of drugs expanded and the need for some method of regulation emerged.

• however, no drug regulatory agency appeared until a century ago !

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History .. continued

• 1820 : Eleven doctors set up the U.S. Pharmacopeia and record the first list of standard drugs.

• 1905 : The American Medical Association (AMA) begins a voluntary program of drug approval that would last until 1955.

• In order to advertise in the AMA and related journals, drug companies must show proof that the drug will treat what they claim.

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The era of FDA…

• The FDA was established in 1906 .

• Before that, most drugs were available without a prescription. just about anything could be put in a bottle and sold as a sure-fire cure. Alcohol, cocaine, marijuana, and opium were included in some OTC products without notification to users.

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a tragedy accelerated things!

• 1937 - Elixir Sulfanilamide, contain the poisonous liquid, diethylene glycol, kills 107 persons, many of whom are children, dramatizing the need to establish drug safety before marketing and to pass the pending food and drug law.

• 1938 - Congress passes The Federal Food, Drug, and Cosmetic (FDC) Act of 1938, which requires that new drugs show safety before selling.

FDA states that sulfanilamide and other dangerous drugs must be given under the direction of a medical expert. This begins the requirement for prescription only (nonnarcotic) drugs.

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Bottom line…

• From this point on, drugs are classified into :• prescription only drugs.• over the counter (OTC) drugs.

• Further amendments limit sale of drugs that cannot be used safely without medical supervision while All other drugs are to be available without a prescription.

• The FD&C Act of 1962 : OTC drugs were required to be both effective and safe.

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Other drug-regulatory agencies

• International• International Conference on Harmonisation (ICH) • World Health Organization (WHO)

• Australia• Therapeutic Goods Administration (TGA)

• Palestine , Bahrain , Bangladesh , Bolivia , Brazil , Chile , Egypt , Jordan & Lebanon

• Ministry of Health

• Europe• EU Legislation - Eudralex • European Directorate for the Quality of Medicines and

Healthcare (EDQM) • European Medicines Agency (EMEA) • Heads of Medicines Agencies (HMA)

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Definitions

• Over-the-counter (OTC) drugs are medicines that may be sold directly to a consumer without a prescription from a health care professional.– Drugs that do NOT require a doctor's prescription – Bought off-the-shelf in stores.– 60% of drugs used by Americans are sold OTC,

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Prescription drugs…

• compared to prescription drugs, which may only be sold to consumers possessing a valid prescription. – Prescribed by a doctor, – Bought at a pharmacy,– Prescribed for and intended to be used by one person.

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Me-too drugs

• OTC drugs are usually regulated by active pharmaceutical ingredients (APIs), not final products.

• Thus, Most OTC agents are no more than “me too “ products.

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Why?

A lesser risky business.

Established safety >>> easy to approve.

75 % of all new drugs coming to market are merely imitations of existing medications.

Cheaper than prescription drugs.

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Up until now..

• Approximately 1000 active ingredients are currently in use

• in more than 125,000 over-the-counter medications in the United States,

• with combined annual sales exceeding $18 billion.

• They fall in 80 therapeutic categories.

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A third category ? Maybe!

Behind-the-counter “BTC” drugs.

• In a middle ground between OTC and prescription-only medicines

• designated to be accessed by patients only after discussion with the pharmacist but don’t need doctor’s prescription.

In the last few years , debate arouse on whether or not classify some drugs (e.g.: levonorgestrel , pseudoephedrine) under a third category:

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Other classification systems : UK

• United Kingdom : has a three-tiered classification system:

General Sale List (GSL) – parallel to OTC Pharmacy medicines (P) – parallels BTC (Mebendazole,

painkillers with small amounts of Codeine and pseudoephedrine.)

Prescription Only Medicines (POM) : (most Antibiotics, all Antidepressants and Antidiabetic medications , Oxycodone and Tramadol, Sildenafil (Viagra) and Diazepam (Valium).

Within POM, certain agents with a high abuse/addiction liability are separately scheduled as Controlled Drugs (CD).

e.g.: (Temazepam, and Methadone).

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Australia• Drugs belong to 1 of 5 categories

» Unscheduled/exempt» Schedule 2 (S2) - Pharmacy Medicines» Schedule 3 (S3) - Pharmacist Only Medicines» Schedule 4 (S4) - Prescription Only Medicines» Schedule 8 (S8) - Controlled Drugs

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How does FDA regulate OTC drugs?

• Strict regulation since may 11th 1972.• Market had over 400000 OTC drugs .. regulation

was a tough , long process.

• Drugs were categorized into :• Category I: GRASE• Category II: not GRASE• Category III: cannot determine if safe and

effective.

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So…

Eventually, FDA established a drug monograph for OTC drug approval.

OTC drug monographs are a kind of "recipe book" covering acceptable ingredients, doses, formulations, labeling, and testing.

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NDA vs. OTC Drug Monograph

OTC Monograph Process NDA Process

NO Pre –market approval Pre –market approval

Public process Confidential filling

Active ingredient-specific Drug product-specific

No marketing exclusivity Marketing exclusivity

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Considerations in Reclassifying a Drug as OTC

• Safety Which is a Relative matter. benefits outweigh risks, the potential for misuse and abuse is low.

• Ease of diagnosis and treatment.

• Proper Labeling.

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• The law requires all over the-counter drug labels to have information in a standard format designed to give the user easy-to-find information.

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• Over the last 30 years , 700 drugs were switched from prescription only to OTC category.

• Pseudoephidren hydrochloride 1976 (Histafed)• ibuprofen 1984 (NDA)• Orlistat 2007 (NDA)

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Current status…

• 2011

• No antibiotics are licensed for OTC use except for the purpose of topical use.

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Why are some drugs sold OTC?

• Self-care constitutes the foundation of the healthcare pyramid– According to Consumer Healthcare Products Association (CHPA):

73% Americans would rather treat themselves at home than to see a doctor.

• To decrease prescription medicine treatment gaps .• The term “treatment gap” refers to the number of people

with a condition or disease who need treatment but do not get it.

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Advantages continued…

• you don't have to go see the doctor every time you have a little sniffle or an ache or pain.

» A 2008 study of heartburn sufferers estimated that if OTC medications were not available, there would be an annual increase of approximately 6 million heartburn- related doctor office visits !

• OTC drugs are cheaper .

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More advantages…

• Accessibility and convenience:

Accessibility : the use of OTC medicines for the treatment of conditions that require early intervention to obtain optimal therapeutic effect, such as migraine headaches or cold sores.

OTC products provide location convenience and save time.

the convenience value of choice.

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However, it’s not all good

• “if 1 pill is good then 2 pills should be twice as good”

• Disadvantages of these types of drugs are not the drugs themselves - it's the people!

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They read the label..NOT!

• 90% to 95% of consumers read the Drug Facts label. However,

• most read the label selectively • often pay insufficient attention to the active ingredients and

the safety information. • Even if patients read the label, they may not comprehend it.

• 50% of respondents who reported taking an OTC pain reliever in 2009 were not concerned about potential side effects.

• Only 16% of consumers read the whole label !!!!

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Overuse – e.g.: Aspirin.

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• Misdiagnosis – e.g.: MI may be misdiagnosed with typical Heartburn.

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• Delays in obtaining a correct diagnosis,

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reduced opportunities to receive counseling about possible lifestyle therapies (such as exercise and diet),

over-the-counter use renders it more difficult to study a drug's effects.

poorer compliance (patients view OTC drugs as not "real“ medications! )

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The potential for abuse.

• OTC drugs are supposed to have low abuse potential. However, It’s found uses for people who want to get high !

• Pharming.

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• Drug seeking behaviour: people trick doctors to get prescription-only medicines.

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Examples : cough relievers (Codein) & Cold medicines

• 5% of teens have abused cough medicines to get high in 2009.• They also look for Codein .. Street names for which include "Captain

Cody" and "Cody." • Pseudoephedrine is commonly found in OTC cold drugs, It is abused

by sport players.

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•Tramadol Vs. Paracetamol

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Drug – drug interactions

• OTC drugs might interactive with other prescriptions, foods, or beverages and lead to possible harmful side effects.

• The interactions between drugs and natural medicines are much less researched and the results of such research are harder to find.

• Read the label!

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Example : Aspirin

• Aspirin increases the bloodsugar-lowering effects of diabetes medicines. (chlorpropamide, Insulin).

• Aspirin gets in the way of the anti-seizure drugs binding with proteins in the blood and leads to increased antiseizure drug levels in your blood. (Valoproic acid, Phenytoin).

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Suicide and accidental death (accidents)

• Abuse of OTCs is most common in adolescents aged 12 to 17 years.• They are 18 times more likely to die from an OTC overdose than

from an illicit drug overdose

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•Painkillers

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• Painkillers , oxycodone and hydrocodone, sleep aid temazepam and sedatives diazepam (AKA Valium), alprazolam (AKA Xanax) and doxylamine.

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Alvis has left the building…

• As many as 14 different drugs, including codeine .

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Resistance to ABs

• The second most common OTC drug in Gaza Strip is Amoxicillin.

• The shocking results: E. coli resistance to amoxicillin reached 97.9%, to piperacillin 78.3%, to doxycycline 90%, to sulfamethoxazole/trimethoprim 63.9% and to cefaclor 42.2%.

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OTC Drugs References

• Textbooks

• Orange book: the List of Approved Drug Products with Therapeutic Equivalence Evaluations By FDA.

• Handbook of Nonprescription Drugs by American Pharmacists Association.

• BNF

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Examples …

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Over-the-counter Viagra

• In UK, The anti-impotence drug Viagra is available without a prescription from 14 February 2007. (Valentine’s day)

• Available for Men aged between 30 and 65.

• They’ll be able to buy four pills only , for £50 after a consultation with the pharmacist.

• Hour-long consultation.

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Static on Statins

• Atorvastatin (Lipitor) : 2008 sales of US $12.4 billion, it was the top-selling branded pharmaceutical in the world.

• Since July 2000, manufacturers of statins have petitioned the FDA to switch the drug category from prescription to over-the-counter (Rx-to-OTC) status.

• To date, their actions have been unsuccessful.

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Why??

• statins are highly effective in reducing cholesterol in most patients, but their use

• requires a clinician’s diagnosis • and careful monitoring of blood levels• have the potential to be highly toxic to the liver.

This contradicts two of the main criteria for the Rx-to-OTC switch.

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Thalidomide

• To pregnant women as an anti-morning sickness pill.• In 1957 it was approved As OTC, advertised for as “completely

safe” for everyone as its developers “could not find a dose high enough to kill a rat.”

• Between 1956 - 1962, roughly 12,000 children were born with severe malformations, and a countless number of thalidomide associated miscariages.

• The drug was banned in the early 1960 s.′

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Tylenol recall

• In 2010, 60 Million OTC Medications Recalled: Tylenol, Motrin, Benadryl, Aspirin, Rolaids recalled by McNeil-PPC after receiving complaints of an "unusual moldy, musty or mildew-like" odor.

• Some patients reported nausea, stomach pain, vomiting and diarrhea.

• the smell was caused by the presence of small amounts of the chemical 2,4,6-tribromoanisole (TBA)- a chemical that is sometimes applied to wood that is used to build wood pallets.

• The FDA has issued a warning letter to McNeil.

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OTC drugs and pregnancy

• It has been estimated that about 50% of products taken during pregnancy are OTC medications.

• Our info regarding this particular field is still limited.

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• Most information we get about safety in pregnancy often comes from practical experience with the medicine over time.

Often, when a medicine has been in wide use for many years without causing adverse effects on pregnancies,

Or from women who have been accidentally exposed to a medicine during pregnancy and from animal studies.

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Examples…

• cimetidine (used for treatment of peptic ulcer) inhibits microsomal enzymes and has been reported to produce fetal liver toxicity when used in late pregnancy.

• Aspirin & salicylate drugs should only be used under doctor's supervision, especially during last trimester.

• They may prolong pregnancy cause excessive bleeding before & after delivery.

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What to do?

• Only take drugs (OTC and prescription) under doctor’s supervision.

• READ THE LABEL REALLY CAREFULLY.

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How to use OTC drugs?

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OTC—Obey The Checklist:

• Always read and follow directions on the OTC Drug Facts label

• Choose an OTC medicine that treats only the problem you have

• If your medicine is causing a side effect speak to your doctor or another healthcare professional.

• If you have any questions or concerns about an OTC medicine ask a health care professional.

• Don't use expired medicines.

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What is Doctor’s part in this?

• Education• Education• Education• Gain patient’s trust.

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Situation in Gaza

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OTC drugs in Gaza…

• Study by J.H Hammad et.al• It assessed the OTC status in Gaza strip from the pharmacists

point of view for the first time in Gaza strip . • sample consisted of 127 pharmacists .• The results showed that most of pharmacists in Gaza strip

prescribe many of the prescription only drugs without any valid prescription.

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What drugs are most commnly prescribed?

0% 20% 40% 60% 80% 100% 120%

Insulin

Digoxin

Enalapril

Amlodipine

Metformin

Prednisone

Glibenclamide

Salbutamol

Gentamicin

Pseudoephedrine

Dexamethasone

Sildenafil

Omeprazole

Ciprofloxacine

Aspirin

Chlorpheniramine

Metronidazole

Diclofenac

Ranitidine

Ibuprofene

Amoxicillin

Paracetamol

Percent of pharmacists who dispense drug without prescription

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• Amoxicillin comes at second place (96% of pharmacist), only after paracetamol, in the list of 22 drugs that are prescribed without valid prescription.

• This is inconsistent with the percentage of 39% of pharmacists who admitted selling non-otc drugs without prescription.

• Drugs for cardiovascular diseases and diabetes mellitus are

prescribed less frequently without valid prescription.

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• study found a strong trend among pharmacists to have regulated drug dispensing policies in community pharmacies.

• most of pharmacists included in this study (89%) believe that the dispensing of prescription only drugs without valid prescription might harm a patient.

• 78% of participant pharmacists encourage a formal policy that regulates the process of drug dispensing in community pharmacies.

• 82% accept punishing steps against pharmacists who dispense

prescription only drug without valid prescription.

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Whose fault?

• The absence of such policies is considered by most of pharmacist as a fault of Ministry of Health ( 77.6% strong fault and 18.4 weak fault),

• pharmacists syndicate (74.2% strong fault and 18.5% weak fault) • colleges of pharmacy (43.7 strong fault and 40.3% weak fault)

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The cause of violation of prescription only drugs

• IT IS A COMPLEX PROBLEM.

0% 20% 40% 60% 80% 100%

Weak trust in primaryhealth care centers

Weak trust inphysicians

Characteristics ofpatient

Poverty of patients

Competition betweenpharmacists

Percent of pharmacists

Weak effect

Strong effect

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Recommendations ?

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