CME PRESENTATION

1. Fatal combination !
Calcium channel blockers plus
Clarithromycin
Dr.Ali Kareem Alnumani
Physician in ROPH
M.B.Ch.B/MRCP UK

2. • The antibiotic clarithromycin
prescribed for patients already
taking antihypertensive ,
calcium-channel blockers is
associated with increases in
hospitalization for acute kidney
injury, hypotension, and death,
according to new research.

3. •Co-prescribing the 2
drugs is a common
practice, despite
warnings of serious
interactions !

4. • "Although the absolute risk increases
were small, these outcomes have
important clinical implications," said
senior author Amit Garg, MD, from
the London Health Sciences Centre
and the University of Western
Ontario.

5. • "Our results suggest that potentially hundreds
of hospitalizations and deaths in our region
may have been associated with this largely
preventable drug–drug interaction," he told
Medscape Medical News. "This burden on the
healthcare system, given the high cost of
managing acute kidney injury, might have
been avoided."
• The results, presented here at Kidney Week
2013, were also published online November 9
in JAMA to coincide with their presentation.

6. •Clarithromycin is an inhibitor of the
cytochrome P453A4, the enzyme
that metabolizes calcium-channel
blockers. Previous research has
shown that the antibiotic can send
blood concentrations of calcium-
channel blockers soaring by as much
as 500%.

7. • Soaring (circulating)Serum Calcium-Channel
Blocker Levels
• A warning from the US Food and Drug
Administration states that "serious adverse
reactions have been reported in patients
taking clarithromycin concomitantly with
CYP3A4 substrates, which includes
hypotension with calcium-channel blockers
metabolized by CYP3A4 (such as verapamil,
amlodipine, diltiazem)."

8. • The reasons for the continued coprescribing of
the drugs, despite the warnings, remain unclear,
said Dr. Garg.
• "We do know that some physicians and
pharmacists are either unaware, or have
remained unconvinced, about the potential
dangers of using these 2 types of drugs together,"
he said.
• In an effort to gauge the extent of serious adverse
clinical events resulting from coprescribing, Dr.
Garg and his team conducted a population-based
retrospective study of older adults in Ontario who
were prescribed the 2 drugs together.

9. • They identified 96,226 adults older than 76
years who were newly prescribed
clarithromycin and 94,083 patients who were
prescribed the alternative, azithromycin, while
taking a calcium-channel blocker such as
amlodipine, felodipine, nifedipine, diltiazem,
or verapamil.
• Because azithromycin is only a weak inhibitor
of CYP34A, the type of intensification of the
calcium-channel blocker that occurs with
clarithromycin is not expected.

10. •The most common
calcium-channel blocker
— amlodipine — was
prescribed to more than
50% of patients.

11. • More Hospitalizations
• Patients coprescribed clarithromycin also had
a higher risk of hospitalization for hypotension
(OR, 1.60) and all-cause mortality (OR, 1.74).
• "Although the absolute risk increases may
have been underestimated due to the limited
sensitivity of the diagnostic codes, we
captured the more severe forms of the
conditions, making these findings of particular
interest to clinicians and policy decision
makers," the researchers report.

12. • A subgroup analysis showed
dihydropyridines, particularly
nifedipine, to be the calcium-channel
blockers associated with the highest
risk (OR, 5.33), with an absolute risk
increase of 0.63%. The risk with
nifedipine was followed by felodipine
and amlodipine

13. •Newer electronic
prescription programs with
built-in interaction
recognition software will
decrease the risk
significantly.

14. • They observed no greater relative risk of
hospitalization, but noted that "the absolute
number needed to harm from the
coprescription was far lower in patients with
chronic kidney disease than in those without."
• Although clarithromycin can be a powerful
antibiotic for challenging infections, clinicians
have easy options for preventing interactions,
said nephrologist Jorge Cerda, MD, from the
Albany Medical College and Capital District
Renal Physicians in New York.

15. •"Clarithromycin may be the top choice for an
antibiotic in some cases, particularly in
patients who are severely immunosuppressed,
such as HIV/AIDS patients, or in the treatment
of extremely drug-resistant bugs," he told
Medscape Medical News. "But in such cases, it
is perfectly feasible to take the patient off the
calcium-channel blocker. You just need to
change the blood pressure medication, which
is easy to do."

16. •"Patients should then have
2 safety mechanisms — at
the time of the e-
prescription, and at the
time of dispensing the drug
by the pharmacist."

17. THANK YOU