케토티펜

Concurrent use /of alcohol, antihistamines, hypnotics, or sedatives/ with /oral/ ketotifen may potentiate the CNS depressant effects of these medications. /Ketotifen fumarate/

Concomitant use /of oral antidiabetic agents/ with /oral/ ketotifen may result in reversible thrombocytopenia ... /Ketotifen fumarate/

... Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs impaired motor coordination in mice treated with valproate, phenobarbital or diphenylhydantoin.

...Ketotifen reduced the protection offered by carbamazepine and elevated the adverse activity of diphenylhydantoin, phenobarbital and valproate /in mice/.

/HUMAN EXPOSURE STUDIES/ Eight patients aged 6 to 34 years took overdoses of ketotifen in doses stated to range from 10 to 120 mg. Plasma concentrations of ketotifen base in 4 patients were 5 to 122 ng per mL (therapeutic range 1to 4 ng per mL) Symptoms included drowsiness, dyspnea, bradycardia or tachycardia, disorientation and convulsions. Gastric lavage was performed in 6 and all recovered within 12 hours after supportive treatment.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

ketotifen

DILI Negative

Opthalmic, Topical

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In female rats treated orally with 2, 10, and 50 mg/kg of ketotifen from day 15 postcoitum to day 21 postpartum, no adverse effects on the pre- and postnatal development of the offspring were found in the two lower dose groups. However, the 50 mg/kg dose produced mortality in 10% of the mothers as well as an increase loss of pups, resulting in slightly decreased litter size and reduced weight gain during the first four days. /Ketotifen fumarate/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In the offspring of the rats that received ketotifen orally from day 15 of pregnancy to day 21 postpartum at a dose of 15 mg/kg per day, the incidence of postnatal mortality was slightly increased, and body weight gain during the first 4 days postpartum was slightly decreased. /Ketotifen fumarate/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Ketotifen caused an increased incidence of retarded ossification of the sternebrae in the offspring of pregnant rabbits that have been given doses of 45 mg/kg per day during organogenesis. However, no effects were observed in rabbits given doses up to 15 mg/kg per day or rats treated with up to 100 mg/kg per day. /Ketotifen fumarate/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In male rats at oral doses >/= 10 mg/kg per day for 70 days prior to mating, ketotifen caused mortality and decreased fertility. In female rats at oral doses of 50 mg/kg per day for 15 days prior to mating, ketotifen did not impair fertility. /Ketotifen fumarate/

/GENOTOXICITY/ Ketotifen fumarate was determined to be non-mutagenic in a battery of in vitro and in vivo mutagenicity assays including: Ames test, in vitro chromosomal aberration test with V79 Chinese hamster cells, in vivo micronucleus assay in mouse, and mouse dominant lethal test.

Treatment of overdose: Treatment is generally symptomatic and supportive, possibly including: If ingestion is very recent, emptying of the stomach may be considered. Administration of activated charcoal may be beneficial. ... If necessary, specific or symptomatic treatment and monitoring of the cardiovascular system and physostigmine for anticholinergic effects are recommended. ... If excitation or convulsions are present, short-acting barbiturates or benzodiazepine may be given. ... Monitor the cardiovascular system. ...

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl ketotifen fumarate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Ketotifen Fumarate/

Ophthalmic: Solution 0.025% Zaditor (with benzalkonium chloride), (Novartis).

Each mL of Zaditor contains: 0.345 mg ketotifen fumarate equivalent to 0.25 mg ketotifen. /Ketotifen Fumarate/

Preparation: J.P. Bourquin, DE 2111071 coresponding to US 3682930 (1971, 1972 both to Sandoz)

Information available in 2004 indicated that Ketotifen was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Bahrain, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Egypt, Iraq, Jordan, Kuwait, Lebanon, Libyan Arab Jamahiriya, Luxembourg, New Zealand, Oman, Poland, Qatar, Romania, Saudi Arabia, Singapore, Spain, Sudan, Syrian Arab Republic, Thailand, Tunisia, Turkey, United Arab Emirates, Yemen, Yugoslavia

Information available in 2004 indicated that Ketotifen fumarate was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belgium, Bermuda, Brazil, Bulgaria, Canada, Cayman Islands, Chile, Colombia, Costa Rica, Cyprus, Czech Republic, Denmark, Dominican Republic, Ecuador, El Salvador, Ethiopia, Finland, France, Germany, Ghana, Greece, Guatemala, Guyana, Haiti, Honduras, Hong Kong, Hungary, India, Indonesia, Iraq, Ireland, Israel, Italy, Jamaica, Jordan, Kenya, Libyan Arab Jamahiriya, Luxembourg, Malaysia, Malta, Mexico, Netherlands, Netherlands Antilles, New Zealand, Nicaragua, Nigeria, Norway, Oman, Panama, Poland, Portugal, Qatar, Romania, Russian Federation, Saudi Arabia, Singapore, Slovenia, South Africa, Spain, Sudan, Sweden, Switzerland, Thailand, Turkey, United Arab Emirates, United Kingdom, United Republic of Tanzania, USA, Yemen, Zimbabwe (1,2) /Ketotifen fumarate/