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WHO Drug Information Vol. 32, No. 1, 2018
Safety news
Safety warnings several hours after administration. In some
patients the onset was after several months
Edoxaban: of treatment.(1)
Interstitial lung disease An overview of the risks of teriparatide
J a p a n – The PMDA has informed health —including hypercalcaemia, a range of
professionals that cases of interstitial side effects due to dilatation of vessels, and
pneumonia have been observed in patients osteosarcoma reported in animal toxicity
treated with the anti-clotting agent studies and leading to suspension of initial
edoxaban (Lixiana®) in Japan. Based on clinical trials—has been published in the
the PMDA’s investigation the MHLW has independent drug bulletin of the Japan
recommended updates to the product Institute of Pharmacovigilance. The authors
information of this medicine. Patients conclude that the benefit/risk balance is
should be carefully monitored. If signs negative in the treatment of osteoporosis.(2)
and symptoms such as cough, shortness of ►► (1) PMDA Summary of investigation
breath, dyspnoea, fever or abnormal chest results and MHLW Revision of precautions
sound are observed, examinations including (teriparatide acetate, teriparatide genetical
recombination), 11 January 2018.
chest X-ray, chest CT scan, and serum
marker test should be done immediately. (2) Med-Check– The Informed Prescriber
If interstitial lung disease is suspected, (TIP). December 2017; 3(9): 34-5.
administration of edoxaban should be
discontinued and appropriate measures such Clarithromycin:
as administration of corticosteroid taken. Risk of cardiovascular events
►► PMDA Summary of investigation results and U n i t e d S t a t e s o f A m e r i c a – The FDA has
MHLW Revision of precautions, 11 January advised caution in the use of the antibiotic
2018.
clarithromycin in patients with heart disease,
even for short periods. Clarithromycin is
Teriparatide: associated with a potential increased risk of
Shock and loss of consciousness heart problems or death that can occur years
J a p a n – Following reported cases of loss later. This safety issue was first observed in
of consciousness and acute hypotension a large clinical trial, and was confirmed in
in patients treated with the osteoporosis a 10-year follow-up study in patients with
medicine teriparatide in Japan, leading to coronary heart disease.
cardiac arrest and/or respiratory arrest in Health care professionals should weigh
some cases, the PMDA has recommended the benefits and risks of clarithromycin and
that clearer warnings should be added to consider prescribing other antibiotics in
the product information about the risk of patients with heart disease. If such patients
seizures, shock and loss of consciousness are given clarithromycin they should be
associated with the use of teriparatide. These alerted to the risks and advised to seek
events may occur immediately or up to medical care immediately if they experience
18WHO Drug Information Vol. 32, No. 1, 2018 Safety news
any signs and symptoms of a cardiovascular Iomeprol, iohexol:
problems such as a heart attack or stroke. Severe skin reactions
The product information has been updated. J a p a n – Following reports of
►► FDA Drug safety communication, 22 February acute generalized exanthematous
2018. pustulosis (AGEP) in patients treated with
the iodinated contrast media iomeprol
Atezolizumab: and iohexol, the PMDA has recommended
Myocarditis updates to the product information to warn
C a n a d a – The marketing authorization about this potential adverse effect.
holder, in agreement with Health Canada, ►► PMDA Summary of investigation results,
has informed health professionals that severe 13 February 2018.
cases of myocarditis have been reported
in patients treated with the anti-cancer Saccharomyces boulardii probiotics:
medicine atezolizumab (Tecentriq®) in Do not use in critically ill or
clinical trials. Healthcare professionals should immunocompromised patients
monitor patients on atezolizumab for signs E s t o n i a – The marketing authorization
and symptoms of myocarditis. Treatment holder, in agreement with the regulatory
should be withheld in patients with Grade 2 authority of Estonia, has informed health
myocarditis, and permanently discontinued professionals that Saccharomyces boulardii-
in patients with Grade 3 or 4 myocarditis. containing probiotic products should not be
Patients on atezolizumab who develop used in critically ill or immunocompromised
myocarditis should receive corticosteroids patients, as they can cause fungaemia in very
and/or additional immunosuppressive agents rare cases. Also, special care should be taken
as clinically indicated. when handling of S. boulardii medicinal
The Canadian product information has products in the presence of patients mainly
been updated to include this new safety with central venous catheters, but also with
information. peripheral catheters, in order to avoid any
►► Health Canada Advisory, 14 February 2018. contamination by touch and the spread
of microorganisms by air. The product
Lenvatinib: information has been updated to include
Gallbladder inflammation these warnings.(1)
J a p a n – The PMDA has informed health S. boulardii is a replacement for intestinal
professionals that cases of acute cholecystitis flora. It is used for adjuvant symptomatic
have been reported in patients treated treatment of diarrhoea as well as for
with the anti-cancer medicine lenvatinib prophylaxis and treatment of antibiotic-
mesilate (Lenvima®) in Japan and in other associated diarrhoea and recurrence of
countries. Two of the cases observed in Clostridium difficile disease in addition to
Japan had a fatal outcome. A warning has vancomycin and metronidazole. The update
been added to the product information, follows a review and recommendation by the
recommending that patient should be EMA’s Pharmacovigilance Risk Assessment
monitored and appropriate measures taken Committee (PRAC).(2)
—such as stopping the medicine—if any ►► (1) Ravimiamet (Estonian medicines agency).
abnormalities are observed. Safety announcement, 13 February 2018.
(Estonian)
►► PMDA Summary of investigation results and
MHLW Revision of precautions, 11 January 2018. (2) PRAC meeting minutes, September 2017.
19Safety news WHO Drug Information Vol. 32, No. 1, 2018
Artemisia annua soft gel capsules: of a rare type of salmonella associated
Reports of liver damage with kratom-containing capsules, teas
N e w Z e a l a n d – Medsafe has alerted and powders. This underscores the risk
consumers that Artemisia annua extract may that unapproved products, which are not
pose a risk of harm to the liver. A. annua subject to manufacturing controls, may be
extract is marketed in New Zealand as a contaminated with harmful bacteria.
natural dietary supplement for maintaining ►► FDA News release, 21 February 2018.
and supporting joint health and mobility.
The warning follows reports of liver toxicity
received by the Agency’s Centre for Adverse To be withdrawn from the market
Reactions Monitoring (CARM). All the
reports involved patients taking a specific Hydroxyethyl starch:
product presented as soft gel capsules. Since Earlier restrictions not sufficient
the chemical composition of the A. annua E u r o p e a n U n i o n – The EMA has
extract in that product was not disclosed endorsed the recommendation by its
it is not clear if other products containing Pharmacovigilance Risk Assessment
A. annua extract could have similar effects. Committee (PRAC) to suspend the
►► Medsafe Alert communication, 15 February marketing authorizations for hydroxyethyl-
2018. starch solutions for infusion across the EU.
These solutions are used as plasma volume
Mitragyna speciosa (kratom): replacement following acute blood loss to
Opioid-like substance to treat hypovolaemia in case cristalloids are
be recalled in the U.S. not sufficient to stabilize the patient.
U n i t e d S t a t e s o f A m e r i c a – The FDA has Restrictions had been introduced in the
received numerous reports of adverse events EU in 2013 to reduce the risks of these
associated with the use of food supplement products for critically ill patients and those
products containing kratom (Mitragyna with sepsis and kidney injury. The PRAC has
speciosa), including 44 reported deaths. reviewed the results of two drug utilization
Such products are not authorized in the studies together with other available data
U.S. The FDA has encouraged companies and feedback from stakeholders and
supplying kratom-containing products to experts, and has concluded that the earlier
organize a destruction and recall, and to restrictions have not been sufficiently
submit data for evaluation of the products effective.
through the applicable regulatory pathway. ►► EMA Press release, 12 January 2018.
Kratom is a plant that grows in Thailand,
Malaysia, Indonesia and Papua New Guinea. Daclizumab:
The FDA has reviewed data suggesting that Cases of inflammatory brain disorders
compounds in kratom share structural E u r o p e a n U n i o n – The EMA has
similarities with controlled opioid analgesics recommended the immediate suspension
and have significant risks of abuse and and recall of the multiple sclerosis medicine
adverse effects. daclizumab (Zinbryta®). This follows
In addition the FDA and the U.S. Centers 12 cases of serious inflammatory brain
for Disease Control and Prevention (CDC) disorders worldwide, including encephalitis
are monitoring a nationwide outbreak and meningoencephalitis. Three of the
20WHO Drug Information Vol. 32, No. 1, 2018 Safety news
cases were fatal. The company that markets Known risks
the medicine has voluntarily requested the
withdrawal of the marketing authorization Obeticholic acid:
and has informed EMA of its decision to Liver decompensation or failure in
stop ongoing clinical studies. incorrectly dosed patients
No new patients should start treatment U n i t e d S t a t e s o f A m e r i c a – In an update
with daclizumab. Healthcare professionals to its communication of September
should immediately contact patients on 2017, the FDA has added its most
daclizumab and should stop their treatment prominent “Boxed Warning” and other
and consider alternatives. Patients stopping updates to the product information for
treatment must be followed up for at least obeticholic acid (Ocaliva®) to clarify the
6 months.(1) recommendations for screening, dosing and
In November 2017 the EMA had tightened monitoring based on the patient’s Child-
its restrictions on the use of daclizumab Pugh score of liver impairment and any
introduced in July 2017 because of the risk of prior decompensation event. Obeticholic
serious liver damage.(2) Available evidence acid is used for the treatment of primary
also indicates that daclizumab could be biliary cholangitis (PBC), a rare chronic liver
linked to other immune-mediated disorders, disease. It has been incorrectly dosed daily
such as blood dyscrasias, thyroiditis or instead of weekly in patients with moderate
glomerulonephritis. An urgent review is to severe PBC, increasing the risk of serious
under way (see page 26). liver injury. The FDA is also requiring a
►► (1) EMA Press release, 7 March 2017. medication guide for patients.
(2) WHO Drug Information, Issues 3 and 4 of ►► FDA Drug safety communication, 2 February
2017. 2018.
Flupirtine: Loperamide:
Serious liver problems Packaging changes for safe use
E u r o p e a n U n i o n – The EMA’s U n i t e d S t a t e s o f A m e r i c a – Despite
Pharmacovigilance Risk Assessment earlier warnings, the FDA continues
Committee (PRAC) has recommended that to receive reports about serious heart
the marketing authorization for the analgesic problems occurring with excessive doses
flupirtine be withdrawn. Following an earlier of the antidiarrhoeal medicine loperamide.
review, restrictions had been introduced Most cases are linked to abuse or misuse
in 2013 to limit the use of flupirtine to no of loperamide, for example to increase
more than two weeks in patients with acute its euphoric effects by combining it with
pain who could not use other analgesics, other drugs, or to treat symptoms of opioid
subject to weekly liver function tests. These withdrawal. The maximum daily dose of
recommendations have not been sufficiently loperamide for adults approved in the U.S.
followed in clinical practice, and the PRAC is 8 mg per day for over-the-counter use and
could not identify any further measures 16 mg per day for prescription use. The FDA
that would adequately reduce the risk of is working with manufacturers to use blister
liver problems associated with the use of packs or other single dose packaging and to
flupirtine. limit the number of doses in a package.
►► EMA. Article 31 referral: Flupirtine-containing ►► FDA Drug Safety Communication, 30 January
medicinal products. 9 February 2018. 2018.
21Safety news WHO Drug Information Vol. 32, No. 1, 2018
Retinoid-containing medicines: clinical study, which has found that an
Updated measures to avoid use in increased blood concentration of efavirenz
pregnancy, neuropsychiatric disorders was associated with prolongation of the
E u r o p e a n U n i o n – The EMA’s QT interval. The product information for
Pharmacovigilance Risk Assessment efavirenz has been updated.
Committee (PRAC) has recommended The product information approved in the
updated measures to avoid the use of EU and the U.S. states that QTc prolongation
retinoids in pregnancy as they can have has been observed with efavirenz, and that
harmful effects on the unborn child, alternatives to efavirenz should be considered
and to warn about the possible risk of in patients taking other medicine with a
neuropsychiatric disorders. known risk of Torsade de Pointes, and in
The recommended pregnancy prevention patients at increased risk of Torsade de
measures depend on the type of retinoid. Pointes.
Oral medicines containing acitretin, ►► PMDA Summary of investigation results,
alitretinoin or isotretinoin must be used in 13 February 2018.
line with an updated pregnancy prevention
programme, and the marketing authorization Ipilimumab:
holders will conduct a study and a survey to Myositis
assess the effectiveness of the new measures. J a p a n – The PMDA has recommended to
For oral bexarotene and tretinoin, which include a warning about the risk of muscle
are used under strict medical supervision to inflammation (myositis) in the product
treat certain cancers, the current pregnancy information for the skin cancer medicine
prevention measures are considered ipilimumab (Yervoy®) in order to align it
appropriate. For topical retinoids the PRAC with the product information approved in
adopted a precautionary approach: Although the EU and the U.S.
their absorption is very low it could be ►► PMDA Summary of investigation results,
increased by excessive use or skin lesions, and 11 January 2018.
their use is not recommended in pregnancy
or in women planning to have a baby.
A warning about the risk of Nintedanib:
neuropsychiatric disorders, such as Liver injury
depression, anxiety and mood changes, will N e w Z e a l a n d , C a n a d a – The marketing
be added to the prescribing information authorization holders, in agreement
of oral retinoids. These events may be due with Medsafe, have informed health
to the medicine as well as the nature of the professionals that cases of drug-induced
disease itself. No additional warning was liver injury (DILI), including one fatal case,
considered necessary for topical retinoids. have been reported in patients treated with
►► EMA. Article 31 referral: Retinoid-containing nintedanib (Ofev®) in the post-marketing
medicinal products. 9 February 2018. setting.(1, 2) Most of these events occurred
in the first three months of treatment.
Efavirenz: Nintedanib is indicated for the treatment
QT interval prolongation of idiopathic pulmonary fibrosis. The
J a p a n – The PMDA has informed health product information is being updated to
professionals about the outcomes of a reflect the observed increased severity of
22WHO Drug Information Vol. 32, No. 1, 2018 Safety news
DILI and to provide further guidance on the Opioid cough and cold medicines:
monitoring schedule of hepatic laboratory Labelling changes
testing. Similar updates have been included U n i t e d S t a t e s o f A m e r i c a – The FDA
in the product information approved in the is requiring updates to the product
U.S., the EU and Japan. information for prescription cough and
►► (1) Dear Healthcare Professional Letter, posted cold medicines containing codeine or
on Medsafe website on 5 December 2017. hydrocodone to limit the use of these
(2) Health Canada Advisory, 11 January 2018. products to adults 18 years and older and
to provide information about the risks of
Valproate: misuse, abuse, addiction, overdose, death,
Updated measures to avoid use in and slowed or difficult breathing. The
pregnancy updates are based on the outcome of an FDA
E u r o p e a n U n i o n – The EMA’s review communicated in April 2017 and the
Pharmacovigilance Risk Assessment recommendations of an expert panel.
Committee (PRAC) has recommended ►► FDA Drug safety communication, 11 January
additional measures to avoid the use 2018.
of valproate in pregnant women. The
medicine should only be used in women of Idarucizumab:
childbearing age if the conditions of a new Second dose may be needed
pregnancy prevention programme are met. N e w Z e a l a n d – Following the outcome of a
New visual warnings, a patient reminder full cohort study, Medsafe has alerted health
card and updated educational materials professionals that some patients may need a
will also be introduced to warn about the second dose of idarucizumab (Praxbind®) to
risk of malformations and developmental reverse the effects of dabigatran (Pradaxa®).
problems in infants exposed to valproate The timing of the second dose depends on
in the womb. The PRAC recognized that the timing of the recurrence of bleeding
for some pregnant women with epilepsy it and the measurement of the elevated
may not be possible to stop valproate, and coagulation tests. More information
determined that they can continue treatment is shown in the product’s data sheet.
with appropriate specialist care. Idarucizumab is indicated in patients treated
Valproate is used in the EU to treat with dabigatran when rapid reversal of
epilepsy and bipolar disorder. In some dabigatran’s anticoagulant effect is required
EU member states it is also authorized to for emergency surgery/urgent procedures or
prevent migraine headaches. The measures in life-threatening or uncontrolled bleeding.
taken following an earlier review have ►► Medsafe Prescriber Update. March 2018.
not been sufficient to mitigate the risks of 39(1): 2.
valproate in pregnancy. The strengthened
warnings were adopted following a second Gadolinium-based contrast agents
review with wide consultation, including a U n i t e d S t a t e s o f A m e r i c a – Based on results
public hearing. of an additional review the FDA is requiring
►► EMA Press release, 9 February 2018. a new class warning for gadolinium-based
contrast agents, alerting health professionals
and patients to the risks caused by long-
term gadolinium retention in the body. A
23Safety news WHO Drug Information Vol. 32, No. 1, 2018
patient medication guide will be introduced, recommended only in individuals with a past
and manufacturers have been requested to dengue infection, as documented either by a
conduct further human and animal safety diagnostic test or by a documented medical
studies.(1) history of past dengue illness. This follows a
In the EU a final decision on restrictions review of preliminary results provided by the
for linear gadolinium-based contrast agents manufacturer. Further WHO guidance on the
has been published following the conclusion matter is expected no earlier than April 2018.
of the EMA’s regulatory review in July 2017. In 2016 the WHO Strategic Advisory
The restrictions recommended earlier were Group of Experts on Immunization (SAGE)
maintained.(2) had recommended the vaccine for use in
►► (1) FDA Drug safety communication, endemic areas with a seroprevalence over
19 December 2017. 70%.(2) A theoretical elevated risk of dengue
(2) EMA’s final opinion confirms restrictions on in vaccinated seronegative individuals was
use of linear gadolinium agents in body scans. noted, prompting additional research by the
23 November 2017.
manufacturer. Preliminary findings suggest
that the subset of trial participants who had
Interim recommendations not been exposed to dengue virus prior
to vaccination had a higher risk of more
Ulipristal: severe dengue and hospitalizations than
No new treatment courses to be started unvaccinated participants. This increased
E u r o p e a n U n i o n – The EMA’s risk was seen after an initial protective period
Pharmacovigilance Risk Assessment and persisted over the observation period of
Committee (PRAC) has recommended that, up to 66 months after primary vaccination.
pending the outcome of its ongoing review Dengvaxia® has been introduced in
of ulipristal (Esmya®), no patients should subnational programmes in the Philippines
start new or repeat treatment courses with and Brazil targeting about one million
ulipristal for uterine fibroids. In women individuals in total. It is otherwise available
currently on treatment, liver function should on the private market in countries where
be monitored at least once a month. If liver there is a marketing authorization. The
enzyme levels are more than twice the upper manufacturer has proposed a labelling change
limit of normal, treatment should be stopped to the national regulatory authorities in the
and the patient closely monitored, and countries where Dengvaxia® is licensed.
the liver function tests should be repeated ►► (1) WHO. Updated Questions and Answers
2–4 weeks after stopping treatment. related to the dengue vaccine Dengvaxia® and
Ulipristal is under EMA review following its use. 22 December 2017.
reports of serious liver injury, including liver (2) WHO. Dengue vaccine: WHO. position
paper – July 2016. Weekly Epidemiological
failure leading to transplantation. Record, No. 30, 29 July 2016.
►► EMA Press release, 9 February 2018.
Recombinant live-attenuated Radium-223 dichloride:
dengue vaccine Must not be used with abiraterone and
WHO has published its interim position on prednisone / prednisolone
the use of the recombinant, live-attenuated E u r o p e a n U n i o n – The EMA has
dengue vaccine Dengvaxia®.(1) Vaccination is recommended contraindicating the
24WHO Drug Information Vol. 32, No. 1, 2018 Safety news
use of the prostate cancer medicine mycophenolate-containing medicines to
radium-223 dichloride (Xofigo®) with prevent rejection of transplanted organs.
abiraterone (Zytiga®) and prednisone / The previous recommendation that male
prednisolone due to an increased risk of patients should use condoms in addition to
death and fractures. Healthcare professionals their female partners using a highly effective
should stop this combination in men method of contraception has been removed.
currently treated with it and review the Either the male patient or his female partner
treatment for these patients. The safety should use reliable contraception during
and efficacy of radium-223 in combination mycophenolate treatment and for at least
with second-generation androgen receptor 90 days after stopping treatment. Female
antagonists, such as enzalutamide (Xtandi®), patients who can become pregnant must use
have not been established. at least one reliable form of contraception
The contraindication was introduced before, during and for 6 weeks after stopping
by the EMA’s Pharmacovigilance Risk treatment. Two forms of contraception are
Assessment Committee (PRAC) as preferred but no longer mandatory.
a temporary measure in view of the ►► EMA Press release, 15 December 2017.
seriousness of the events reported in a
clinical trial. An in-depth review of the Combination treatments for asthma:
benefits and risks of radium-223 is ongoing. Warning removed
►► EMA Press release, 9 March 2018. U n i t e d S t a t e s o f A m e r i c a – An FDA review
of four large clinical safety trials has shown
that treating asthma with long-acting beta
Warnings softened agonists (LABAs, e.g. salmeterol, vilanterol,
formoterol) in combination with inhaled
Direct-acting antivirals: corticosteroids (ICS, e.g. fluticasone,
Effect on blood glucose not confirmed mometasone, budesonide) does not result
N e w Z e a l a n d – Medsafe has provided an in significantly more serious asthma-related
update on its monitoring communication side effects than treatment with an ICS
issued in March 2017, which highlighted a alone. The Boxed Warning about asthma-
possible blood glucose-lowering effect of related death has been removed from the
the direct acting antivirals Viekira Pak® and product information of medicines that
Viekira Pak-RBV® when used in patients contain both an ICS and LABA.
with type 2 diabetes. No further cases were Using LABAs alone to treat asthma
reported in New Zealand, and the effect without an ICS to treat lung inflammation is
could not be confirmed. associated with an increased risk of asthma-
►► Medsafe monitoring communication, related death. The warnings stating this will
31 January 2018. remain in the product information of the
relevant medicines.
Mycophenolate: ►► FDA Drug safety communication, 20 December
Updated recommendations for 2017.
contraception
E u r o p e a n U n i o n – The EMA has
updated its recommendations for
contraception in men and women taking
25Safety news WHO Drug Information Vol. 32, No. 1, 2018
Reviews started
Medicine Use Concerns Reference
Daclizumab Treatment Cases of serious inflammatory brain ►► EMA Press release,
(urgent of multiple disorders, including 3 fatal cases. Linked 7 March 2017.
review) sclerosis to potentially fatal immune-mediated
(Zinbryta®) liver injury in a 2017 review. Possible risk
of other immune-mediated disorders.
To be recalled (see page 20).
Dabigatran Anti Possible risk of gout or gout-like ►► Medsafe Monitoring
(Pradaxa®) thrombotic symptoms (one case report in New Communication,
31 January 2018.
agent Zealand, and reports in WHO’s VigiBase)
Compliance with good practices integrity and other GMP failures during an
inspection of the company’s site located at
Svizera Labs Pvt Ltd: No. 10, Longhai Avenue, in Qinhuangdao,
Notice of Concern withdrawn Hebei Province, China.
Following corrective actions taken by A WHO inspection of the site in
Svizera Labs Pvt Ltd and the clarifications December 2017 revealed that the company
provided being considered acceptable, and had only partly addressed the FDA’s
considering the outcome of an additional observations. A follow-up WHO inspection
on-site inspection on 25–29 June 2017, the is planned for October 2018 to verify that
WHO Prequalification Team - Medicines has the company has implemented its corrective
withdrawn the Notice of Concern (NOC) and preventive action (CAPA) plan as
for Svizera Labs Pvt Ltd Mumbai, India. The submitted to WHO.
NOC had been issued on 2 September 2015 Qinhuangdao Zizhu manufactures
after an inspection of the company’s site at three prequalified active pharmaceutical
Turbhe, Navi Mumbai, India. ingredients (APIs) – levonorgestrel,
►► WHO Prequalification News, 1 February 2018. mifepristone and ethinylestradiol – and
supplies levonorgestrel for two prequalified
finished products. To date WHO has not
Qinhuangdao Zizhu Pharmaceutical received any complaints relating to the
Co Ltd: quality of prequalified levonorgestrel
Corrective action under way tablets. WHO is working closely with the
G e n e v a – The WHO Prequalification manufacturers of prequalified levonorgestrel
Team–Medicines has provided an update tablets to identify alternative API sources,
on the level of compliance with good and has requested them to take additional
manufacturing practices (GMP) by measures to ensure that all API batches
Qinhuangdao Zizhu Pharmaceutical Co Ltd. from Qinhuangdao Zizhu meet their
On 8 March 2017 the U.S. FDA had placed specifications.
an import alert on the company, following ►► WHO Prequalification Team–Medicines.
observations of serious breaches of data Position paper, 13 February 2018.
26WHO Drug Information Vol. 32, No. 1, 2018 Safety news
Falsified medicines
Falsified cefixime products circulating in the Democratic Republic of
the Congo
The WHO Medical Product Alert No. 1/2018 relates to two versions of falsified cefixime
products that have been identified in the eastern part of the Democratic Republic of the
Congo (South Kivu) and were reported to WHO in late 2017. Cefixime is used to treat a
range of bacterial infections and is listed as a WHO Essential Medicine.
The products were sent for quality assurance laboratory testing and the results shared
with WHO (see table). Both products are presented in standard white plastic containers of
100 tablets. The tablets of both products are round, small, and without any embossing. The
labels of both products have spelling mistakes. Product details are shown below.
Product 1 Product 2
Product name: CEFIXIME Cifixime Trihydrate
Batch number: 4734 Et078776
Expiry date: 12/2019 DEC 2018
Manufacturing date: 01/2016 Nov 2014
Stated active pharmaceutical ingredient: Cefixime Cifixime Trihydrate
Manufacturer name stated on the label: MERCK & CO. INC. HOLDEN MEDICAL
THE NETHERLANDS
2.5% of declared content
Assay result: No cefixime detected
of cefixime
Both stated manufacturers have confirmed they did not manufacture either of these
products. No adverse reactions to either product have been reported to WHO at this stage.
►► WHO Medical Product Alert No. 1/2018 (includes photographs).
Falsified “Augmentin” circulating in Cameroon
The WHO Medical Product Alert No. 2/2018 relates to a falsified version of
Augmentin (amoxicillin + clavulanate potassium) identified in Cameroon. WHO was
informed in early 2018 by an NGO that this product was available in a street market
å
in Douala. The packaging of the falsified product appears to be a close imitation of
the genuine product manufactured by GlaxoSmithKline (GSK). The writing on the
packaging has some spelling errors. GSK has confirmed that they did not manufacture
this product.
Samples were sent for quality assurance testing and the results shared with WHO. The
laboratory analysis did not identify any of the expected active ingredients.
The source of the falsified product has not yet been identified. No adverse reactions
have been reported to WHO at this stage.
►► WHO Medical Product Alert No. 2/2018 (includes photographs).
Report suspected falsified products to the competent national regulatory authority and/or
pharmacovigilance centre, and notify WHO at rapidalert@who.int.
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