MY PIKIN TEETH MIXTURE TRAGEDY: A REPEAT LIKELY IF…

I had thought of reviewing some other medication issues this week but the My Pikin Mixture tragedy kept crying’ for more attention. During this past week, accusations, counter-accusations and new revelations by different agencies and parastatals of the Federal Ministry of Health made this issue to remain on the front burner of the healthcare sector. Interestingly, some callers, in response to my last week write-up were a little bit upset, they accused me of being economical with my conclusion and position rather than asking so many questions, questions that are yet to be addressed by those concerned even as at today. These I hope to clarify in this edition by critically looking at issues that came up during the past week.

How big is this problem?

As I have already maintained, this is a national tragedy and disaster that requires an emergency response. In a country where most patients do not have access to modern healthcare, the level of reported health issues to the authorities is better imagined. This is why some of us believe that the 55 reported cases in the My Pikin mixture tragedy is just an understatement. Unfortunately, the symptoms of diethylene glycol poison are similar to what people consider as ‘spiritual attack’ in our local environment. This may have been the conclusion of some of these innocent parents by discharging their children against medical advise as reported during the week.

The statement by the Lagos University Teaching Hospital (LUTH’s) Chief Medical Director (CMD), Prof Akin Osibogun that My Pikin Mixture may not be the only cause of the infant deaths should not be taken lightly. According to the investigations of the LUTH’s team, 43 percent of the deaths admitting using My Pikin Mixture were related to the use of the drug. This, logically, suggests that something else may be responsible for the cases of the other 53 percent deaths that manifested the same symptoms as those that took My Piken Mixture. My guess is that other brands of teething mixtures are out there in the markets that may be equally Harmful.

Furthermore, according to investigations so far conducted by NAFDAC in 33 states, 2,057 bottles of My Pikin Mixture were recovered. “Out of the total, 255 bottles of batch 02008 (the contaminated batch) were recovered. A total number of My Pikin retrieved from across the country is 425 bottles; 297 from Rivers State, 81 from Kaduna State and 47 from Lagos.”

If the batch size of My Pikin was 3000 products and NAFDAC was only able to retrieve 255 bottles, we still have over 2,400 poisonous My Pikin Mixture either in circulation or already consumed. Unfortunately, drug distribution system in the country is chaotic and unstructured. This is where I will want to agree with the President of the Pharmaceutical Society of Nigeria, Mr. Anthony Akhimen fired from all cylinders during the week. Mr. Akhimen berated the government over the chaotic drug distribution system that does not permit an audit trail procedure for recalling spurious products.

“Unless government’s attitude is changed and the open drug markets spread across the nation are dismantled immediately, the nation would experience a repeat of the present death saga which may be worse than what we have ever experienced,” he said.

Let me deviate a little bit to respond to specifics issues by our healthcare agencies;

From Lagos University Teaching Hospital, LUTH

According to Chief Medical Director (CMD) of the Lagos University Teaching Hospital (LUTH’s) Prof Akin Osiboguno “We are working with a team of epidemiologists from the FMOH and Lagos State Ministry of Health (LSMH). We do not have any problem with NAFDAC, but they did not share information with us. After coming here and got that 43 per cent of the children were taking My Pikin and with their own findings, they went to press without informing the Minister of Health or us. They are supposed to share information with us. We gave them some samples to go and test. But one thing that must be made clear is that all the federal agencies are working together.’

From Nigerian Association of Industrial Pharmacists (NAIP)

In the words of the National Chairman of Nigerian Association of Industrial Pharmacists (NAIP), Emmanuel Ekunno, the handling of the episode by everyone, including the NAFDAC, “has been unnecessarily sensational rather than being scientific.’

National Agency For Food And Drug Admin. and Control, NAFDAC

“The reporting system, whereby LUTH wrote to the Minister of Health when this situation broke out is not the best for our system when we even have pharmacovigilance centre in such hospitals. LUTH is supposed to report straight to us when the problem started, so that we will be swift in addressing it to forestall more deaths.

“Unfortunately, they wrote to the Ministry of Health. Government carved out NAFDAC from the Ministry of Health’s Drug and Food Directorate in 1993 to eliminate such administrative bottlenecks so that the agency can act swiftly and more efficiently on food and drug issues and report activities to the Minister, who can advise.

When one reads between the lines, it appears some agencies are just ready to justify their innocence in the national tradegy. LUTH in my opinion did what was right and followed procedures by laying a report to the Ministry which unfortunately did not escalate the necessary actions and processes. One good thing we can take out of this is that eveybody has realised the importance of collectively moving forward.

“Where did the ethylene glycol come from?

This was the big question asked by the Director General of NAFDAC. According to her “It is not possible to plant people in any factory. What we do is that before registration, we test and retest. After registration, we go to the factory in Nigeria and abroad in such cases on independent unannounced audits of factories.”

“We have not given any company permit to import diethylene glycol. The chemical used in My Pikin must have been smuggled. We are investigating the case and will get to the root of this matter”.

“Right now, we are testing other brands of paracetamol syrup from all over the country to ensure that none is contaminated with diethyleneglycol. NAFDAC staff have also moved to the local governments and villages for the mopping up process of My Pikin teething mixture.

“We have also put in our standard operating procedures that any diethyleneglycol for production of paracetamol and similar drugs must be screened by NAFDAC before use in production, no matter how sophisticated the company’s quality assurance system may be”.

One must commend NAFDAC for the swift way they moved into the appropriate segment to desiminate information to parents. My little boy came home with a newlsetter from his school with a well crafted alert from NAFDAC on this issue. This is highly commendable. However, it appears to be another grandstanding that the agency is known for when it talks of controlling the use of diethylene glycol. The fact that diethelne glycol is not a food or pharmaceutical excipient puts it outside the regulatory scope of NAFDAC. I wonder how they intend to do this.

What should we do?

1. We should Improve on the regulation of the sales of Pharmaceutical raw materials, both active and excipients

2. Restrict licencing for sale of chemicals to two broad groups; Food and Drugs and Industrial so that people do not play simultaneously in the two lines of Business.

1. NAFDAC should have a structured programme to survey ALL products post-registration on an annual basis.

4. NAFDAC should immediately randomely assay all Paracetamol preparation in Nigeria.

1. Compel all registered manufacturers of pcm syrup to submit their holding stock for assay,

1. All pharmaceuticals companies should immediately subject the ‘propylene glycol ‘in their possession to the appropriate test and notify NAFDAC with the quantity, date and place of purchase.

Most of us have now been vindicated that the insistence on Nafdac no, and the hologram do not prevent or deter drug adultration. These are just media and pubicity grand standing which in the long run will not benefit the common man.

While commending the effort so far made by nafdac, one thing should be made clear. And that is that no body is contesting with NAFDAC for visibility. The agency should learn to work with other agencies, parastatals of government and other stakeholders.

In all, one fact is obvious; the product and the factory of Barewa Pharmaceuticals, the company that manufactured My Pikin were certified by NAFDAC. Since the last audit was in August, it is possible that the contaminated product was manufactured around the time of the last audit. It is certain that once a product has been approved by NAFDAC, there is absolutely no reason for any pharmacy or teaching hospital to analyse it before purchase. This last saga, to my mind is a very big indictment of NAFDAC’s product licensing capacity. Millions of people have now lost confidence in the reliabilty of NAfDAC No. on any product.

ADVICE TO PATIENT

Paracetamol

For the patient, the options available are;

1. Use Paracetamol Suspension.

2. For older children (between 3-6years) one may use the tablets, sometimes broken into two depending on the age

3. Where available, use children’s paracetamol tablets

4. Stop the use of any teething formulation or paracetamol syrup until the situation is clearer.

5. Report any case of difficulties in urinating, fever etc to your nearest pharmacy or hospital

CHILD’S TEETHING PROBLEMS, MY PIKIN TEETHING MIXTURE AND WHERE MOTHERS GOT IT WRONG

Dateline 1990, locations, University of Jos Teaching Hospital and the University College Hospital, Ibadan; 109 Children died after administration of Paracetamol Syrup. This was 57 years after the infamous 1937 Elixir Sulphanilamide disaster in the United States of America in which 107 people died after taking sulphanilamide dissolved in diethylene glycol.

Eighteen years after, My Pikin Teething Mixture, a product registered by NAFDAC may have been fingered as the ‘killer‘ drug that has claimed the lives of not less than 25 children. The drug is manufactured by Barewa Pharmaceuticals Limited, a certified manufacturer by NAFDAC. The national drug law enforcer has, however, shut down the company in the wake of the death allegedly in consequence of the administration of the drug.

Barewa, has, since then, spiritedly defended the contents of My Pikin Teething Mixture as a Paracetamol based drug containing Paracetamol B.P. 120 mg and Diphenhydramine HCL B.P. 6.25 mg per 5mls. But a preliminary test carried out by the National Agency for Food and Drug Administration and Control, has revealed that besides Paracetamol, the drug contains Diethylene glycol as against propylene glycol which is the commonly used excipient. Incidentally, Diethelyne glycol was also implicated in the 1990 deaths in Jos and Ibadan

What is more worrisome with this type of poisoning is the fact that the original chemical entity, Paracetamol is naturally poisonous to the kidneys and liver in high doses. Marry this with the toxicity of Diethylene glycol, what do you have? Bomb!! Instant death.

These, however, are 25 deaths too many. While we await the report of more detailed investigations from the appropriate authorities, so many questions are begging for answers;

Is the drug registered by NAFDAC?

Is the factory currently certified by NAFDAC?

When was the last audit of the factory carried out by NAFDAC?

When was the last time NAFDAC independently surveyed this particular drug in the market?

Has NAFDAC a structured process/procedure to routinely carry on surveillance on ALL products in the market or does the agency randomly pick products?

What do all the agencies, LUTH, UCH, NAFDAC want to achieve by ‘issuing alert’? What in specific terms have they done? What have they put in place to ensure positive outcome? What has been the distribution route of all products from this factory in the last Three months?

Does this ‘alert’ consider the chaotic nature of our drug distribution channels which the Pharmaceutical Society of Nigeria has been talking about over the last several years?

Over the years, regulatory bodies have scaled up their regulatory oversight on pharmaceutical excipients. Pharmaceutical excipients – are inactive ingredients used to formulate active ingredients into finished dosage forms

“…For example, excipients can:

• aid in the processing of the drug delivery system during its

manufacture,

• protect, support or enhance stability, bioavailability or patient

acceptability,

• assist in product identification, or

• enhance any other attribute of the overall safety, effectiveness

or delivery of the drug during storage or use…”

It may interest the Nigerian public to know that since 2007, European regulatory agencies have initiated steps to improve the quality and regulatory aspects of all excipients used in pharmaceutical products all over Europe because of the risks associated with pharmaceutical excipients. Some of the documented evidence of risk includes:

• Fraudulent product obtained from broken supply chain and distribution routes leading to contamination cases and tragedies as outlined below:

1990 Nigeria: Cough syrup contaminated with solvents (47 reported deaths)

1986-1998 India and Bangladesh: Paracetamol syrup contaminated with diethylene glycol from propylene glycol origins (236 reported deaths)

1996 Haiti: Glycerine contaminated with diethylene glycol (88 reported deaths)

Potential exposure:

• Use of inappropriate grade of materials for critical route of administration (e.g. pyrogene-free requirements)

• Excipient variability between suppliers

It is a known general requirement of Good Pharmaceutical Manufacturing Practise to analyse ALL inputs to the production process. We need to know what is contained in the production process submitted by the company while registering My Pikin Mixture as submitted by the company and approved by NAFDAC. Is this process complied with by the manufacturer?

Some pharmacists have long questioned the rational for our regulatory body to continue to register teething formulations. Teething is a well known non specific condition that is common with children and the usual practise is to symptomatically manage the child.

‘We are confronted with cases of mothers using various teething formulations at once usually resulting in a child taking about 4X the dose of paracetamol’ says a colleague during our brain storming section on Teething mixtures some Six months ago. Cases abound where mothers administer these teething formulations (which usually contain Paracetamol 120mg/5ml) with standard Paracetamol syrup. This health risk is further compounded as they are both Over The Counter (OTC) medicines without regulatory restriction/control of use. While this school of thought has spoken against the outright ban of Paracetamol, some have advocated more stringent packaging alert and warning to parents

This should not be the time for agencies and institutions to trade blames or to start defending themselves. The Federal government should consider these deaths a national tragedy. The loss of defenceless innocent children is not taken lightly in countries where citizens are considered supreme

One thing is clear, the way NAFDAC is currently constituted underscores the fact the agency is a reactionary agency. The agency should be reformed to anticipate problems and prevent them from happening. Life is too precious to be treated the way we currently do, particularly that of Innocent Children

It is the responsibility of the Federal Government to protect the health of the Nigerian Population and I believe that this is one of the reasons NAFDAC was set up. Parents should not just take this as another case of an ‘act of God.’ They should consider this as another case of the carelessness of the state through her agencies against the citizen. This may just be an opportunity for the victims to challenge this callous act through our judicial process. This may just be the wake up call we need to usher in a new healthcare system that really cares for the Nigerian citizens

The dry weather is back again. This is usually the period for high prescription of chloramphenicol eye drop. Has this been prescribed for you. Below is the prescribed way to administer it for maximum benefit.

ADVICE TO PATIENTS

(1) Chloramphenicol Eye Drop;

1. Chlopramphenicol is an antibiotic used to treat eye infection.

2. It is important to use this eye drop as frequently and for as long as the doctor has prescribed and advised by your pharmacist.

3. Do not wear contact lenses while using this drug.

4. If using two drops, for each dose wait for a minute or two between applying the first and second drop. Using more than two drops will not help because the excess will run out of your eye.

5. Pressing your finger against the inner corner of the eye (by the nose) for about a minute after using the drops can help to stop the drops draining into your nose and throat.

6. Discard any unused and left over content three (3) weeks after opening.

7. You may feel a brief stinging after using this eye drop. If this is prolonged for more than three days or your eyes do not get better please see your doctor or pharmacist.