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DRUG INTERACTIONS
Based upon the results of in vitro human microsome
studies, there is low likelihood of drug–drug interactions. In vitro studies using human liver microsomes indicate that
cytochrome P450 isoenzymes are not involved in the metabolism of lubiprostone.
Further in vitro studies indicate microsomal carbonyl
reductase may be involved in the extensive biotransformation of lubiprostone to
the metabolite M3 (See Pharmacokinetics
[12.3].). Additionally, in vitro studies in human liver microsomes demonstrate that
lubiprostone does not inhibit cytochrome P450 isoforms 3A4, 2D6, 1A2, 2A6, 2B6,
2C9, 2C19, or 2E1, and in vitro studies of primary
cultures of human hepatocytes show no induction of cytochrome P450 isoforms 1A2,
2B6, 2C9, and 3A4 by lubiprostone. No drug–drug interaction studies have been
performed. Based on the available information, no protein binding–mediated drug
interactions of clinical significance are anticipated.
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OVERDOSAGE
There have been two confirmed reports of overdosage with Amitiza. The first
report involved a 3-year-old child who accidentally ingested 7 or 8 capsules of
24 mcg of Amitiza and fully recovered. The second report was a study patient who
self-administered a total of 96 mcg of Amitiza per day for 8 days. The patient
experienced no adverse reactions during this time. Additionally, in a Phase 1
cardiac repolarization study, 38 of 51 patients given a single oral dose of 144
mcg of Amitiza (6 times the highest recommended dose) experienced an adverse
event that was at least possibly related to the study drug. Adverse reactions
that occurred in at least 1% of these patients included the following: nausea
(45%), diarrhea (35%), vomiting (27%), dizziness (14%), headache (12%),
abdominal pain (8%), flushing/hot flash (8%), retching (8%), dyspnea (4%),
pallor (4%), stomach discomfort (4%), anorexia (2%), asthenia (2%), chest
discomfort (2%), dry mouth (2%), hyperhidrosis (2%), and syncope (2%).
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CONTRAINDICATIONS
Amitiza is contraindicated in patients with known or suspected mechanical
gastrointestinal obstruction.
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