The following serious adverse reactions are described
elsewhere in the labeling:
- Hypersensitivity [See CONTRAINDICATIONS]
- Myasthenia Gravis [See WARNINGS AND PRECAUTIONS]
- Clostridium difficile-associated diarrhea [See WARNINGS
Clinical Trials Experience
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in practice.
In clinical trials using triple therapy with omeprazole,
clarithromycin, and amoxicillin, no adverse reactions unique to triple therapy were
observed. Adverse reactions observed were limited to those previously reported
with omeprazole, clarithromycin, or amoxicillin alone. The most frequent
adverse reactions observed in clinical trials using combination therapy with
omeprazole, clarithromycin, and amoxicillin (n = 274) were diarrhea (14%), taste
perversion (10%), and headache (7%). None of these occurred at a higher
frequency than that reported by patients taking antimicrobial agents alone.
Adverse Reactions From Labeling For The Individual
Components Of Omeclamox®-Pak
The safety data below reflect exposure to omeprazole
delayed-release capsules and clarithromycin worldwide in clinical trials for various
indications using doses and durations of therapy that may differ from how they
are used as a component of Omeclamox®-Pak. For complete information on these
reactions, see the full prescribing information for omeprazole delayed-release
capsules and clarithromycin.
The most common adverse reactions reported (i.e., with an
incidence rate ≥ 2%) in 3096 patients from omeprazole delayed-release capsules-treated
patients enrolled in clinical trials included headache (6.9%), abdominal pain
(5.2%), nausea (4.0%), diarrhea (3.7%), vomiting (3.2%), and flatulence (2.7%).
Additional adverse reactions that were reported with an
incidence rate ≥ 1% included acid regurgitation (1.9%), upper respiratory
infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), asthenia
(1.3%), back pain (1.1%), and cough (1.1%).
The clinical trial safety profile in patients greater
than 65 years of age was similar to that in patients 65 years of age or less.
The most frequently reported events in adults were
diarrhea (3%), nausea (3%), abnormal taste (3%), dyspepsia (2%), abdominal pain/discomfort
(2%), and headache (2%). Most of these events were described as mild or
moderate in severity. Of the reported adverse events, only 1% were described as
severe. Fewer than 3% of adult patients without mycobacterial infections
discontinued therapy because of drug-related side effects.
[See ADVERSE REACTIONS]
Post-Marketing Experience With The Individual Components Of
Because these reactions are voluntarily reported from a
population of uncertain size, it is not always possible to reliably estimate
their actual frequency or establish a causal relationship to drug exposure.
Body As a Whole: Hypersensitivity reactions
including anaphylaxis, anaphylactic shock, angioedema, bronchospasm,
interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue;
Cardiovascular: Chest pain or angina, tachycardia,
bradycardia, palpitations, elevated blood pressure, peripheral edema.
Gastrointestinal: Pancreatitis (some fatal),
anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal
atrophy of the tongue, stomatitis, abdominal swelling, dry mouth. During
treatment with omeprazole, gastric fundic gland polyps have been noted rarely.
These polyps are benign and appear to be reversible when treatment is discontinued.
Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison
syndrome on long-term treatment with omeprazole. This finding is believed to be
a manifestation of the underlying condition, which is known to be associated
with such tumors.
Hepatic: Liver disease including hepatic failure
(some fatal), liver necrosis (some fatal), hepatic encephalopathy
hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and
elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and
Metabolic/Nutritional: Hypoglycemia, hyponatremia,
Musculoskeletal: Muscle weakness, myalgia, muscle
cramps, joint pain, leg pain.
Nervous System/Psychiatric: Psychiatric and sleep
disturbances including depression, agitation, aggression, hallucinations,
confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream
abnormalities; tremors, paresthesia; vertigo.
Respiratory: Epistaxis, pharyngeal pain.
Skin: Severe generalized skin reactions including
toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, and erythema
multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus;
petechiae; purpura; alopecia; dry skin; hyperhidrosis.
Special Senses: Tinnitus, taste perversion.
Ocular: Optic atrophy, anterior ischemic optic
neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred
vision, double vision.
Urogenital: Interstitial nephritis, hematuria,
proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract
infection, glycosuria, urinary frequency, testicular pain.
Hematologic: Agranulocytosis (some fatal),
hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia,
Hypersensitivity Reactions: Allergic reactions
ranging from urticaria and mild skin eruptions to rare cases of anaphylaxis,
Stevens- Johnson syndrome, and toxic epidermal necrolysis have occurred.
Gastrointestinal: Glossitis, stomatitis, oral
moniliasis, anorexia, vomiting, pancreatitis, tongue discoloration.
Hematologic: Thrombocytopenia, leukopenia,
Other: There have been reports of tooth
discoloration in patients treated with clarithromycin. Tooth discoloration is
usually reversible with professional dental cleaning.
Nervous System/Psychiatric: There have been
isolated reports of hearing loss, which is usually reversible, occurring
chiefly in elderly women. Reports of alterations of the sense of smell, usually
in conjunction with taste perversion or taste loss have also been reported.
Transient CNS events including anxiety, behavioral
changes, confusional states, convulsions, depersonalization, disorientation, hallucinations,
insomnia, manic behavior, nightmares, psychosis, tinnitus, tremor, dizziness
and vertigo have been reported during postmarketing surveillance. Events
usually resolve with discontinuation of the drug.
Hepatic: Hepatic dysfunction, including increased
liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without
jaundice, has been infrequently reported with clarithromycin. This hepatic
dysfunction may be severe and is usually reversible. In very rare instances,
hepatic failure with fatal outcome has been reported and generally has been
associated with serious underlying diseases and/or concomitant medications.
Metabolic: There have been rare reports of
hypoglycemia, some of which have occurred in patients taking oral hypoglycemic
agents or insulin.
Cardiac: As with other macrolides, clarithromycin
has been associated with QT prolongation and ventricular arrhythmias, including
ventricular tachycardia and torsades de pointes.
Renal: There have been reports of interstitial
nephritis coincident with clarithromycin use.
Gastrointestinal: Nausea, vomiting, diarrhea, and
hemorrhagic/Clostridium difficile-associated colitis. Onset of Clostridium
difficileassociated diarrhea may occur during or after antibiotic treatment
[See WARNINGS AND PRECAUTIONS].
Hypersensitivity Reactions: Serum sickness like
reactions, erythematous maculopapular rashes, erythema multiforme, Stevens- Johnson
syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized
exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been
reported. Reactions are more likely to occur in individuals who have previously
demonstrated hypersensitivity to penicillins and in those with a history of
allergy, asthma, hay fever, or urticaria.
Hepatic: A moderate rise in AST (SGOT) and/or ALT
(SGPT) has been noted, but the significance of this finding is unknown. Hepatic
dysfunction including cholestatic jaundice, hepatic cholestasis and acute
cytolytic hepatitis have been reported.
Renal: Crystalluria has also been reported [See OVERDOSAGE].
Hemic and Lymphatic Systems: Anemia, including
hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia
and agranulocytosis have been reported during therapy with penicillins. These
reactions are usually reversible on discontinuation of therapy and are believed
to be hypersensitivity phenomena.
Nervous System/Psychiatric: Reversible
hyperactivity, agitation, anxiety, insomnia, confusion, behavioral changes,
and/or dizziness have been reported rarely.
Miscellaneous: Tooth discoloration (brown, yellow,
or gray staining) has been rarely reported. Most reports occurred in pediatric patients.
Discoloration was reduced or eliminated with brushing or dental cleaning in
Changes in Laboratory Values
laboratory values with possible clinical significance were as follows: Hepatic
– elevated SGPT (ALT) less than 1%, SGOT (AST) less than 1%, GGT less than 1%,
alkaline phosphatase less than 1%, LDH less than 1%, total bilirubin less than
1%; Hematologic – decreased WBC less than 1%, elevated prothrombin time 1%;
Renal – elevated BUN 4%, elevated serum creatinine less than 1%. GGT, alkaline
phosphatase, and prothrombin time data are from adult studies only.