Oral chemotherapy – use as directed

Carien van der Merwe debunks the misconceptions that patients have about oral chemotherapy drugs, and highlights the dangers of non-adherence of these medications.

My mom turns 80 next year. She is still with-it and travels on her own overseas to visit my sisters. Of course, she is forgetful and repeats a story more than once as is expected of people that age. On a recent trip, she planned to stay for over a month. Her repeat medication gets delivered to her each month, but seeing she would need more, she requested that I get it for her. I counted her pills to establish exactly how many she would need. Her blood pressure tablets were short of 15 tablets; the rest of her tablets all correlated. Visiting the pharmacy, the pharmacist told me she got all her tablets as one refill. So where were the 15 missing tablets? My world stopped. Did she take them by mistake?

As a pharmacist, I am used to the jokes, the stories and anecdotes about wrong labelling and patients’ white lies as to why they took their pills the way they did. According to the American Society on Aging (ASA) and the American Society of Consultant Pharmacists Foundation (ASCP), non-adherence of medication accounts for more than 10% of older adult hospital admissions, nearly one-fourth of nursing home admissions, and 20% of preventable adverse drug events among older persons in the ambulatory setting.     It is estimated that medication non-adherence results in 125,000 deaths annually, and costs the US healthcare system $100-$300 billion per year.

Being an oncology pharmacist, I am acutely aware of the increase of oral chemotherapy agents in use. Oral chemotherapeutic drugs have been available for decades, and include the familiar agents chlorambucil (Leukeran), cyclophosphamide (Endoxan), methotrexate, and 6-mercaptopurine (Purinethol). In 1995, only six oral chemotherapy agents were available, in 2007 about 12, and today more than 40 oral chemotherapy agents are registered by the FDA. Adherence of cancer patients may be higher than other chronic disease patients because cancer patients are “highly motivated” by the gravity of their disease, and have “too much to lose” by being non-adherent.

Patient preference for oral chemotherapy may be based on the incorrect assumption that oral therapy is associated with minimal side effects; some patients may incorrectly assume that oral chemotherapy is not “real” chemotherapy and is similar to taking a vitamin or antibiotic. This dangerous misconception may also be the rationale for the preference of oral chemotherapy in frail elderly patients.

Patients must understand that oral equivalents of cytotoxic therapies, such as capecitabine (Xedola), have side effects that are similar to their parenteral counterparts. The need to monitor for side effects and change dosages increases the complexity of oral chemotherapy regimens. For example, many oncologists can relate examples of patients who began to experience toxicity from capecitabine on a Friday, but didn’t consult a physician over the weekend. If these patients continue on the same dosage, either because they don’t recognise the incipient side effects, such as severe vomiting, or because they don’t want to compromise the effectiveness of their chemo, they may have a life-threatening level of toxicity by Monday.

Also, from the patient’s perspective, an oral regimen may not be simple to administer. Instructions for capecitabine may include:

• Take with water within 30 minutes of a meal.

• If a dose is missed, do not take the drug when remembered, and do not take a double dose.

• Stop taking capecitabine and contact the doctor, if experiencing four or more bowel movements than usual per day, diarrhoea at night, loss of appetite or large reduction in fluid intake, more than one vomiting episode in 24 hours, pain, redness, or swelling of hands or feet that prevents normal activity.

Another common misperception is that oral drugs have a broader therapeutic index and thus are safer than parenteral drugs. The therapeutic index is based on the class of drug and its mechanism of action, not the route of administration.

Medication adherence is defined by the World Health Organisation (WHO) as “the degree to which the person’s behaviour corresponds with the agreed recommendations from a healthcare provider.” Compliance is the extent to which a patient’s behaviour matches the prescriber’s advice.

The term ‘concordance’ was first formally defined by a working party of the Royal Pharmaceutical Society of Great Britain (RPSGB) in 1997. It refers to an agreement reached after negotiation between a patient and a health professional, who respects the beliefs and wishes of the patient in determining whether, when and how medicines are to be taken. Although concordance is reciprocal, it is an alliance in which the health professional recognises the primacy of the patient’s decisions about taking the recommended medications. It is about patients being empowered to manage   their own life and to be satisfied with a consultation.

In a study by Weingart et al, (Cancer, 2010), on oral chemotherapy medication errors, reports were collected on oral chemotherapy-associated medication errors from medical literature and Internet search and review of reports to the Medication Errors Reporting Programme (MERP) and incidents reports from 15 comprehensive cancer centres. The authors identified 99 adverse drug events, 322 near misses, and 87 medical errors with low-risk of harm.

Of the 99 adverse drug events, 20 were serious or life-threatening, 52 were significant, and 25 were minor. The most common medication errors involved wrong dose (38,8%), wrong drug (13,6%), wrong number of days supplied (11%), and missed dose (10%). The majority of errors resulted in a near miss; however, 39,3% of reports involving the wrong number of days supplied resulted in adverse drug events.

Oral cytototoxic drugs are not harmless, not non-toxic and not without any problems. There is an absolute need of explanations on dispensing, especially with the first dose.

Please look at the general dos and don’ts when handling oral cytototoxic drugs:


• Ensure that you completely

understand when and how to take your


• Understand that it is chemotherapy and could harm people and the environment.

• Transport and store medicine as instructed.

• Wash your hands before and after taking/touching your tablets. If a caregiver is giving it to you, they must also wash their hands and use gloves. Alternatively, they can tip tablets and capsules from the container pack directly into a disposable medicine cup.

• Report any overdosing immediately.

• Know the symptoms that could lead to life-threatening adverse effects of the particular drug.

• Know the start and stop dates.

• Know if you need to avoid certain foods.

• Drink a lot of fluids, if this is a requirement.

• Keep a journal of adverse effects. Have a list of adverse effects for which the healthcare team has to be contacted immediately.

• Return wet, damaged, unused, discontinued, or expired medicine to the pharmacist.


• Crush, break or chew your medicine.

• Store your medicine in areas where food or drinks are stored, unless told to do so.

• Leave your medicine in open areas near water or direct sunlight.

• Leave medicine where it can be accessed by children or pets.

• Double up on doses, if you have missed a dose.

• Take doses on days instructed not to take your medicine.

• Push medicine out of sealed packaging into other containers.

• Share your medication with anyone.

• Skip doses unless instructed by your physician.

• Discard medication down the toilet or in the garbage.

I recently dispensed cortisone tablets to two of my oncology patients. One had to take 80 tablets per day for seven days; the other patient had to take 40 tablets on day 1, 8, 15 and 22. Both received these before and it was a mere repeat fill. I was amazed by their non-adherence, when questioning them on how they take their tablets. I realised that it is not just if a patient is non-adherent, but how a patient is non-adherent.

A lot of the pharma companies invest in supplying a booklet with their oral chemotherapy drug, explaining the taking of the drug and/or supplying items to aid with side effect management. There are also interesting tools available on the web to assist healthcare professionals (See Oncology Nurses Society Oral Adherence Took Kit).

It is time to change oncology practices – to incorporate a dedicated team and dedicated time to explain oral treatments, and supply literature to aid adherence to avoid explanations in hallways and in front of other patients to obtain clear, honest feedback from patients.

The patient needs to understand and make the decision to take the responsibility of adherence despite the side effect profile. More emphasis should be on assisting the burden of co-payments and financial difficulty, often encountered in mostly costly oral targeted chemotherapy.

I still worry about my mum, but not as much as unpacking a parcel, dispensed by a courier pharmacy, destined to a patient receiving oral chemotherapy labelled “use as directed” without a warning label stating it is chemotherapy.


Carien van der Merwe is an oncology pharmacist and has 12 years of experience in oncology pharmacy, paediatric and adult. She has been involved with chemotherapy training to ensure higher standards within the work flow of the oncology pharmacy units, and has travelled extensively in Africa evaluating and tutoring oncology pharmacy for trial sites in Uganda, Malawi, Zimbabwe, Nigeria, Tanzania and Kenya.