A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Prevpac Side Effects, and Drug Interactions - Lansoprazole, Amoxicillin And Clarithromycin
Prevpac Side Effects, and Drug Interactions - Lansoprazole, Amoxicillin And Clarithromycin
SIDE EFFECTS
The most common adverse reactions ( ≥3%) reported in clinical trials when
all three components of this therapy were given concomitantly for 14 days are
listed in the table below.
Adverse Reactions Most Frequently Reported
in Clinical Trials ( ≥3%)
|
|
Triple Therapy |
|
Adverse Reaction
|
n=138
(%) |
|
Diarrhea
|
7.0 |
|
Headache
|
6.0 |
|
Taste Perversion
|
5.0 |
The additional adverse reactions which were reported as possibly or probably
related to treatment (<3%) in clinical trials when all three components of
this therapy were given concomitantly are listed below and divided by body system:
Body as a Whole abdominal pain; Digestive System dark stools,
dry mouth/thirst, glossitis, rectal itching, nausea, oral moniliasis, stomatitis,
tongue discoloration, tongue disorder, vomiting; Musculoskeletal System myalgia;
Nervous System confusion, dizziness; Respiratory System respiratory
disorders; Skin and Appendages skin reactions; Urogenital System
vaginitis, vaginal moniliasis. There were no statistically significant
differences in the frequency of reported adverse events between the 10- and
14-day triple therapy regimens.
PREVACID:
The following adverse reactions from the labeling for lansoprazole are provided
for information.
Worldwide, over 6100 patients have been treated with lansoprazole in Phase
2-3 clinical trials involving various dosages and durations of treatment. In
general, lansoprazole treatment has been well tolerated in both short-term and
long-term trials.
Incidence in Clinical Trials
The following adverse events were reported by the treating physician to have
a possible or probable relationship to drug in 1% or more of patients treated
with PREVACID capsules and occurred at a greater rate in patients treated with
PREVACID capsules than placebo-treated patients:
Incidence of Possibly or Probably
Treatment-Related Adverse Events in Short-term,
Placebo-Controlled Studies
|
Body System/Adverse Event
|
PREVACID
(N=1457)
% |
Placebo
(N=467)
% |
|
Body as a Whole
|
|
Abdominal Pain
|
1.8 |
1.3 |
|
Digestive System
|
|
Diarrhea
|
3.6 |
2.6 |
|
Nausea
|
1.4 |
1.3 |
Headache was also seen at greater than 1% incidence but was more common on placebo.
The incidence of diarrhea is similar between placebo and lansoprazole 15 mg
and 30 mg patients, but higher in the lansoprazole 60 mg patients (2.9%, 1.4%,
4.2%, and 7.4%, respectively).
The most commonly reported possibly or probably treatment-related adverse event
during maintenance therapy was diarrhea.
Additional adverse experiences occurring in <1% of patients or subjects
in domestic trials are shown below.
Refer to Postmarketing for adverse reactions occuring since the
drug was marketed.
Body as a Whole asthenia, candidiasis, chest pain (not otherwise specified),
edema, fever, flu syndrome, halitosis, infection (not otherwise specified),
malaise; Cardiovascular System angina, cerebrovascular accident, hypertension/hypotension,
myocardial infarction, palpitations, shock (circulatory failure), vasodilation;
Digestive System anorexia, bezoar, cardiospasm, cholelithiasis, constipation,
dry mouth/thirst, dyspepsia, dysphagia, eructation, esophageal stenosis, esophageal
ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic
gland polyps, gastroenteritis, gastrointestinal hemorrhage, hematemesis, increased
appetite, increased salivation, melena, rectal hemorrhage, stomatitis, tenesmus,
ulcerative colitis, Endocrine System diabetes mellitus, goiter, hyperglycemia/hypoglycemia;
Hemic and Lymphatic System anemia, hemolysis; Metabolic and Nutritional
Disorders gout, weight gain/loss; Musculoskeletal System arthritis/arthralgia,
musculoskeletal pain, myalgia; Nervous System agitation, amnesia, anxiety,
apathy, confusion, depression, dizziness/syncope, hallucinations, hemiplegia,
hostility aggravated, libido decreased, nervousness, paresthesia, thinking abnormality;
Respiratory System asthma, bronchitis, cough increased, dyspnea, epistaxis,
hemoptysis, hiccup, pneumonia, upper respiratory inflammation/infection; Skin
and Appendages acne, alopecia, pruritus, rash, urticaria; Special Senses
blurred vision, deafness, eye pain, otitis media, taste perversion, tinnitus,
visual field defect; Urogenital System abnormal menses, albuminuria,
breast enlargement/gynecomastia, breast tenderness, glycosuria, hematuria, impotence,
kidney calculus.
Postmarketing
Ongoing Safety Surveillance: Additional adverse experiences have been reported
since lansoprazole has been marketed. The majority of these cases are foreign-sourced
and a relationship of lansoprazole has not been established. Because these events
were reported voluntarily from a population of unknown size, estimates of frequency
cannot be made. These events are listed below by COSTART body system.
Body as a Whole anaphylactoid-like reaction; Digestive System hepatotoxicity,
vomiting; Hemic and Lymphatic System agranulocytosis, aplastic anemia,
hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and
thrombotic thrombocytopenic purpura; Special Senses speech disorder;
Urogenital System urinary retention.
Laboratory Values
The following changes in laboratory parameters were reported as adverse events.
Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT),
increased creatinine, increased alkaline phosphatase, increased globulins, increased
GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia,
eosinophilia, hyperlipemia, increased/decreased electrolytes, increased/decreased
cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal
platelets, and increased gastrin levels. Additional isolated laboratory abnormalities
were reported.
In the placebo-controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated,
0.4% (1/250) placebo patients and 0.3% (2/795) lansoprazole patients had enzyme
elevations greater than three times the upper limit of normal range at the final
treatment visit. None of these patients reported jaundice at any time during
the study.
Amoxicillin:
The following adverse reactions from the labeling for amoxicillin are provided
for information.
As with other penicillins, it may be expected that untoward reactions will
be essentially limited to sensitivity phenomena. They 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.
The following adverse reactions have been reported as associated with the use
of penicillin:
Gastrointestinal Glossitis, stomatitis, black "hairy" tongue, nausea,
vomiting, and diarrhea. (These reactions are usually associated with oral dosage
forms.)
Hypersensitivity Reactions Skin rashes and urticaria have been reported
frequently. A few cases of exfoliative dermatitis and erythema multiforme have
been reported. Anaphylaxis is the most serious reaction experienced and has
usually been associated with the parenteral dosage form. Note: Urticaria,
other skin rashes, and serum sickness-like reactions may be controlled with
antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions
occur, penicillin should be discontinued unless, in the opinion of the physician,
the condition being treated is life threatening and amenable only to penicillin
therapy. Serious anaphylactic reactions require the immediate use of epinephrine,
oxygen, and intravenous steroids.
Liver A moderate rise in serum glutamic oxaloacetic transaminase (SGOT)
has been noted, particularly in infants, but the significance of this finding
is unknown.
Hemic and Lymphatic Systems Anemia, thrombocytopenia, thrombocytopenic
purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during
therapy with the penicillins. These reactions are usually reversible on discontinuation
of therapy and are believed to be hypersensitivity phenomena.
Clarithromycin:
The following adverse reactions from the labeling for clarithromycin are provided
for information.
The majority of side effects observed in clinical trials were of a mild and
transient nature. Fewer than 3% of adult patients without mycobacterial infections
discontinued therapy because of drug-related side effects.
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% was described as severe.
Postmarketing Experience:
Allergic reactions ranging from urticaria and mild skin eruptions to rare cases
of anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have
occurred. Other spontaneously reported adverse events include glossitis, stomatitis,
oral moniliasis, anorexia, vomiting, tongue discoloration, thrombocytopenia,
leukopenia, neutropenia, and dizziness. There have been reports of tooth discoloration
in patients treated with clarithromycin. Tooth discoloration is usually reversible
with professional dental cleaning. 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,
depersonalization, disorientation, hallucinations, insomnia, manic behavior,
nightmares, psychosis, tinnitus, tremor, and vertigo have been reported during
postmarketing surveillance. Events usually resolve with discontinuation of the
drug.
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.
There have been rare reports of hypoglycemia, some of which have occurred in
patients taking oral hypoglycemic agents or insulin.
As with other macrolides, clarithromycin has been associated with QT prolongation
and ventricular arrhythmias, including ventricular tachycardia and torsades
de pointes.
Changes in Laboratory Values: Changes in laboratory values
with possible clinical significance were as follows: Hepatic elevated
SGPT (ALT) <1%, SGOT (AST) <1%, GGT <1%, alkaline phosphatase <1%,
LDH <1%, total bilirubin <1%; Hematologic decreased WBC <1%,
elevated prothrombin time 1%; Renal elevated BUN 4%, elevated serum
creatinine <1%. GGT, alkaline phosphatase, and prothrombin time are from
adult studies only.
DRUG INTERACTIONS
PREVACID:
PREVACID is metabolized through the cytochrome P 450 system, specifically
through the CYP3A and CYP2C19 isozymes. Studies have shown that PREVACID does
not have clinically significant interactions with other drugs metabolized by
the cytochrome P 450 system, such as warfarin, antipyrine, indomethacin,
ibuprofen, phenytoin, propranolol, prednisone, diazepam, clarithromycin, or
terfenadine in healthy subjects. These compounds are metabolized through various
cytochrome P 450 isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6,
and CYP3A. When PREVACID was administered concomitantly with theophylline (CYP1A2,
CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because
of the small magnitude and the direction of the effect on theophylline clearance,
this interaction is unlikely to be of clinical concern. Nonetheless, individual
patients may require additional titration of their theophylline dosage when
PREVACID is started or stopped to ensure clinically effective blood levels.
PREVACID has also been shown to have no clinically significant interaction
with amoxicillin.
In a single-dose crossover study examining PREVACID 30 mg and omeprazole 20
mg each administered alone and concomitantly with sucralfate 1 gram, absorption
of the proton pump inhibitors was delayed and their bioavailability was reduced
by 17% and 16%, respectively, when administered concomitantly with sucralfate.
Therefore, proton pump inhibitors should be taken at least 30 minutes prior
to sucralfate. In clinical trials, antacids were administered concomitantly
with PREVACID Delayed-Release Capsules; this did not interfere with its effect.
PREVACID causes a profound and long-lasting inhibition of gastric acid secretion;
therefore, it is theoretically possible that PREVACID may interfere with the
absorption of drugs where gastric pH is an important determinant of bioavailability
(eg, ketoconazole, ampicillin esters, iron salts, digoxin).
Clarithromycin:
Clarithromycin use in patients who are receiving theophylline may be associated
with an increase of serum theophylline concentrations. Monitoring of serum theophylline
concentrations should be considered for patients receiving high doses of theophylline
or with baseline concentrations in the upper therapeutic range. In two studies
in which theophylline was administered with clarithromycin (a theophylline sustained-release
formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500
mg q12h clarithromycin), the steady-state levels of C max , C min
, and the area under the serum concentration time curve (AUC) of theophylline
increased about 20%.
Concomitant administration of single doses of clarithromycin and carbamazepine
has been shown to result in increased plasma concentrations of carbamazepine.
Blood level monitoring of carbamazepine may be considered.
When clarithromycin and terfenadine were coadministered, plasma concentrations
of the active acid metabolite of terfenadine were threefold higher, on average,
than the values observed when terfenadine was administered alone. The pharmacokinetics
of clarithromycin and the 14-hydroxy-clarithromycin were not significantly affected
by coadministration of terfenadine once clarithromycin reached steady-state
conditions. Concomitant administration of clarithromycin with terfenadine is
contraindicated. (See CONTRAINDICATIONS .)
Spontaneous reports in the postmarketing period suggest that concomitant administration
of clarithromycin and oral anticoagulants may potentiate the effects of the
oral anticoagulants. Prothrombin times should be carefully monitored while patients
are receiving clarithromycin and oral anticoagulants simultaneously.
Elevated digoxin serum concentrations in patients receiving clarithromycin
and digoxin concomitantly have also been reported in postmarketing surveillance.
Some patients have shown clinical signs consistent with digoxin toxicity, including
potentially fatal arrhythmias. Serum digoxin levels should be carefully monitored
while patients are receiving digoxin and clarithromycin simultaneously.
For information on interactions between clarithromycin in combination with
other drugs which may be administered to HIV-infected patients, see the BIAXIN
package insert, Drug Interactions, under the PRECAUTIONS section.
The following drug interactions, other than increased serum concentrations
of carbamazepine and active acid metabolite of terfenadine, have not been reported
in clinical trials with clarithromycin; however, they have been observed with
erythromycin products and/or with clarithromycin in postmarketing experience.
Concurrent use of erythromycin or clarithromycin and ergotamine or dihydroergotamine
has been associated in some patients with acute ergot toxicity characterized
by severe peripheral vasospasm and dysesthesia.
Erythromycin has been reported to decrease the clearance of triazolam and,
thus, may increase the pharmacologic effect of triazolam. There have been
postmarketing reports of drug interactions and CNS effects (e.g., somnolence
and confusion) with the concomitant use of clarithromycin and triazolam.
There have been reports of an interaction between erythromycin and astemizole
resulting in QT prolongation and torsades de pointes. Concomitant administration
of erythromycin and astemizole is contraindicated. Because clarithromycin
is also metabolized by cytochrome P 450 , concomitant administration
of clarithromycin with astemizole is not recommended.
As with other macrolides, clarithromycin has been reported to increase concentrations
of HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin), through
inhibition of cytochrome P 450 metabolism of these drugs. Rare
reports of rhabdomyolysis have been reported in patients taking these drugs
concomitantly.
The use of erythromycin and clarithromycin in patients concurrently taking
drugs metabolized by the cytochrome P 450 system may be associated
with elevations in serum levels of these other drugs. There have been reports
of interactions of erythromycin and/or clarithromycin with carbamazepine,
cyclosporine, tacrolimus, hexobarbital, phenytoin, alfentanil, disopyramide,
lovastatin, bromocriptine, valproate, terfenadine, cisapride, pimozide, rifabutin,
and astemizole. Serum concentrations of drugs metabolized by the cytochrome
P 450 system should be monitored closely in patients concurrently
receiving these drugs.
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