CONTRAINDICATIONS
Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin,
erythromycin, or any of the macrolide antibiotics.
Concomitant administration of clarithromycin with cisapride, pimozide, or terfenadine is
contraindicated. There have been post-marketing reports of drug interactions when clarithromycin
and/or erythromycin are co-administered with cisapride, pimozide, or terfenadine resulting in cardiac
arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de
pointes) most likely due to inhibition of hepatic metabolism of these drugs by erythromycin and
clarithromycin. Fatalities have been reported.
For information about contraindications of other drugs indicated in combination with clarithromycin,
refer to the CONTRAINDICATIONS section of their prescribing information.
WARNINGS
CLARITHROMYCIN SHOULD NOT BE USED IN PREGNANT WOMEN EXCEPT IN
CLINICAL CIRCUMSTANCES WHERE NO ALTERNATIVE THERAPY IS
APPROPRIATE. IF PREGNANCY OCCURS WHILE TAKING THIS DRUG, THE
PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS.
CLARITHROMYCIN HAS DEMONSTRATED ADVERSE EFFECTS OF
PREGNANCY OUTCOME AND/OR EMBRYO-FETAL DEVELOPMENT IN
MONKEYS, RATS, MICE, AND RABBITS AT DOSES THAT PRODUCED PLASMA
LEVELS 2-17 TIMES THE SERUM LEVELS ACHIEVED IN HUMANS TREATED AT
THE MAXIMUM RECOMMENDED HUMAN DOSES. (See PRECAUTIONS,
Pregnancy.)
Pseudomembranous colitis has been reported with nearly all antibacterial agents,
including clarithromycin, and may range in severity from mild to life threatening.
Therefore, it is important to consider this diagnosis in patients who present with diarrhea
subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth
of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of
“antibiotic-associated colitis”.
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should
be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug
alone. In moderate to severe cases, consideration should be given to management with fluids and
electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective
against Clostridium difficile colitis.
For information about warnings of other drugs indicated in combination with clarithromycin, refer to
the WARNINGS section of their prescribing information.
PRECAUTIONS
General
Clarithromycin is principally excreted via the liver and kidney. Clarithromycin may be administered
without dosage adjustment to patients with hepatic impairment and normal renal function. However,
in the presence of severe renal impairment with or without coexisting hepatic impairment,
decreased dosage or prolonged dosing intervals may be appropriate.
Clarithromycin in combination with ranitidine bismuth citrate therapy is not recommended in patients
with creatinine clearance less than 25 ml/min. (See DOSAGE AND ADMINISTRATION.)
Clarithromycin in combination with ranitidine bismuth citrate should not be used in patients with a
history of acute porphyria.
For information about precautions of other drugs indicated in combination with clarithromycin, refer
to the PRECAUTIONS section of their prescribing information.
Information for the Patient
Clarithromycin tablets and oral suspension can be taken with or without food and can be taken with
milk. Do NOT refrigerate the suspension.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
The following in vitro mutagenicity tests have been conducted with clarithromycin:
Salmonella/Mammalian Microsomes Test.
Bacterial Induced Mutation Frequency Test.
In Vitro Chromosome Aberration Test.
Rat Hepatocyte DNA Synthesis Assay.
Mouse Lymphoma Assay.
Mouse Dominant Lethal Study.
Mouse Micronucleus Test.
All tests had negative results except the In Vitro Chromosome Aberration Test which was weakly
positive in one test and negative in another.
In addition, a Bacterial Reverse-Mutation Test (Ames Test) has been performed on clarithromycin
metabolites with negative results.
Fertility and reproduction studies have shown that daily doses of up to 160 mg/kg/day (1.3 times the
recommended maximum human dose based on mg/m2) to male and female rats caused no adverse
effects on the estrous cycle, fertility, parturition, or number and viability of offspring. Plasma levels
in rats after 150 mg/kg/day were 2 times the human serum levels.
In the 150 mg/kg/day monkey studies, plasma levels were 3 times the human serum levels. When
given orally at 150 mg/kg/day (2.4 times the recommended maximum human dose based on mg/m2),
clarithromycin was shown to produce embryonic loss in monkeys. This effect has been attributed to
marked maternal toxicity of the drug at this high dose.
In rabbits, in utero fetal loss occurred at an intravenous dose of 33 mg/m2, which is 17 times less
than the maximum proposed human oral daily dose of 618 mg/m2.
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of
clarithromycin.
Pregnancy, Teratogenic Effects, Pregnancy Category C
Four teratogenicity studies in rats (3 with oral doses and 1 with intravenous doses up to 160
mg/kg/day administered during the period of major organogenesis) and 2 in rabbits at oral doses up
to 125 mg/kg/day (approximately 2 times the recommended maximum human dose based on
mg/m2) or intravenous doses of 30 mg/kg/day administered during gestation days 6-18 failed to
demonstrate any teratogenicity from clarithromycin. Two additional oral studies in a different rat
strain at similar doses and similar conditions demonstrated a low incidence of cardiovascular
anomalies at doses of 150 mg/kg/day administered during gestation days 6-15. Plasma levels after
150 mg/kg/day were 2 times the human serum levels. Four studies in mice revealed a variable
incidence of cleft palate following oral doses of 1000 mg/kg/day (2 and 4 times the recommended
maximum human dose based on mg/m2, respectively) during gestation days 6-15. Cleft palate was
also seen at 500 mg/kg/day. The 1000 mg/kg/day exposure resulted in plasma levels 17 times the
human serum levels. In monkeys, an oral dose of 70 mg/kg/day (an approximate equidose of the
recommended maximum human dose based on mg/m2) produced fetal growth retardation at plasma
levels that were 2 times the human serum levels.
There are no adequate and well-controlled studies in pregnant women. Clarithromycin should be
used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See
WARNINGS.)
Nursing Mothers
It is not known whether clarithromycin is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when clarithromycin is administered to a
nursing woman. It is known that clarithromycin is excreted in the milk of lactating animals and that
other drugs of this class are excreted in human milk. Preweaned rats, exposed indirectly via
consumption of milk from dams treated with 150 mg/kg/day for 3 weeks, were not adversely
affected, despite data indicating higher drug levels in milk than in plasma.
Pediatric Use
Safety and effectiveness of clarithromycin in pediatric patients under 6 months of age have not
been established. The safety of clarithromycin has not been studied in MAC patients under the age
of 20 months. Neonatal and juvenile animals tolerated clarithromycin in a manner similar to adult
animals. Young animals were slightly more intolerant to acute overdosage and to subtle reductions
in erythrocytes, platelets and leukocytes but were less sensitive to toxicity in the liver, kidney,
thymus, and genitalia.
Geriatric Use
In a steady-state study in which healthy elderly subjects (age 65-81 years old) were given 500 mg
every 12 hours, the maximum serum concentrations and area under the curves of clarithromycin
and 14-OH clarithromycin were increased compared to those achieved in healthy young adults.
These changes in pharmacokinetics parallel known age-related decreases in renal function. In
clinical trials, elderly patients did not have an increased incidence of adverse events when compared
to younger patients. Dosage adjustment should be considered in elderly patients with severe renal
impairment.