Ketotifen

309.43

309.43

252-099-7

X49220T18G

DTXSID7023190

C61799

Crystals from ethyl acetate

S01GX08|R - Respiratory system|S - Sensory organs

48.6 Ų

log Kow= 3.85 /Estimated/|2.2

1.236

152-153 °C

488.9±45.0 °C(Predicted)

In water, 15.3 mg/L at 25 °C /Estimated/|7.87e-03 g/L

4.2X10-8 mm Hg at 25 °C /Estimated/

8.84±0.20

Henry's Law constant= 3.2X10-11 atm-cu m/mole at 25 °C /Estimated/

8.43

Hydroxyl radical reaction rate constant= 2.1X10-10 cu cm/molecule-sec at 25 °C /Estimated/

No rapid reaction with air. No rapid reaction with water.

Amines, Phosphines, and Pyridines

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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/

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Adverse reactions include headaches, conjunctival injection and rhinitis.

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/.

75%

It is not known whether ophthalmic ketotifen is absorbed in sufficient quantities to be distributed into human breast milk. However, it has been found in the milk of nursing rats following oral administration. /Ketotifen fumarate/

Indicated as an add-on or prophylactic oral medication in the chronic treatment of mild atopic asthmatic children. Also used as self-medication for the temporary relief of itching of the eye due to allergic conjunctivitis (ophthalmic).|FDA Label

Oral ketotifen is indicated as an add-on medication in the chronic treatment of mild atopic asthmatic children. Ketotifen is a prophylactic agent to be used on a continuous basis and is not effective in the acute prevention or treatment of acute asthma attacks. /Not commercially available in US/|Ophthalmic ketotifen is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis. /Included in US product labeling/

Ketotifen should not be used to treat contact lens related irritation. /Ketotifen fumarate/|Pregnancy risk category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|Symptoms of central nervous system stimulation, such as excitation, irritability, insomnia, and nervousness have been observed, particularly in children. /Ketotifen fumarate (systemic)/|For patients with diabetes: Recognizing that ketotifen syrup contains 4 g of carbohydrate in every 5 mL; glucose concentrations may be affected. /Ketotifen fumarate (systemic)/|For more Drug Warnings (Complete) data for KETOTIFEN (9 total), please visit the HSDB record page.

Ketotifen is a fast acting non-competitive histamine antagonist. It inhibits the release of mediators from mast cells. It is a non-bronchodilator antiasthmatic drug (when taken orally).

Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. (See all compounds classified as Histamine H1 Antagonists.)|Agents, usually topical, that relieve itching (pruritus). (See all compounds classified as Antipruritics.)|Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475) (See all compounds classified as Anti-Allergic Agents.)

Following oral administration absorption is at least 60%|Within 48 hours, urinary excretion amounts to 1% as unchanged drug and 60% to 70% as metabolites. Clearance is higher in children. /Ketotifen fumarate/|Following oral administration absorption is at least 60% ... The rate of absorption is rapid with an absorption half life of 1 hour. Bioavailability is about 50%, due to a large first pass effect. Bioavailability is not affected by the intake of food. /Ketotifen fumarate/|... A study conducted with 15 healthy volunteers dosed bilaterally with ketotifen fumarate ophthalmic solution twice daily for 14 days demonstrated plasma concentrations generally below the quantitation limit of assay (< 20 pg/mL). /Ketotifen fumarate/|It is not known whether ophthalmic ketotifen is absorbed in sufficient quantities to be distributed into human breast milk. However, it has been found in the milk of nursing rats following oral administration. /Ketotifen fumarate/|For more Absorption, Distribution and Excretion (Complete) data for KETOTIFEN (7 total), please visit the HSDB record page.

Primarily hepatic. The main metabolite found in both plasma and urine is the inactive ketotifen-N-glucuronide. Nor-ketotifen, the N-demethylated metabolite, and the 10-alpha-hydroxyl derivative are the only other metabolites detectable in human urine.|The main metabolite found in both plasma and urine is the inactive ketotifen-N-glucuronide. Nor-ketotifen, the N-demethylated metabolite, and the 10-hydroxyl derivative are the only other metabolites detectable in human urine. Both the 10-hydroxyl derivative and N-glucuronide conjugate may reform the intact product by in vivo reversibility. The pattern of metabolism in children over the age of 3 years is the same as in adults, but the clearance is higher in children. /Ketotifen fumarate (systemic)/|Ketotifen has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[1-methyl-4-(8-oxo-6-thiatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-2-ylidene)piperidin-1-ium-1-yl]oxane-2-carboxylic acid and Ketotifen N-glucuronide.

21 hours (for elimination)|Distribution: 3 to 5 hours. Elimination: 21 hours. /Ketotifen fumarate (systemic)/|... The rate of absorption /following oral administration/ is rapid with an absorption half life of 1 hour.

Ketotifen is a relatively selective, non-competitive histamine antagonist (H1-receptor) and mast cell stabilizer. Ketotifen inhibits the release of mediators from mast cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils have also been demonstrated. Ketotifen also inhibits cAMP phosphodiesterase. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include inhibition of the development of airway hyper-reactivity associated with activation of platelets by PAF (Platelet Activating Factor), inhibition of PAF-induced accumulation of eosinophils and platelets in the airways, suppression of the priming of eosinophils by human recombinant cytokines and antagonism of bronchoconstriction due to leukotrienes. Ketotifen inhibits of the release of allergic mediators such as histamine, leukotrienes C4 and D4(SRS-A) and PAF.|Ketotifen is a non-bronchodilator antiasthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. Ketotifen possesses a powerful and sustained non-competitive histamine (H1) blocking property. Ketotifen's antihistamine (H1) effect seems to be distinct from it antiallergic properties. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include: In Vivo results: Inhibition of the development of airway hyperreactivity associated with activation of platelets by PAF (Platelet Activating Factor) or caused by neural activation following the use of sympathomimetic drugs or the exposure to allergen; inhibition of PAF-induced accumulation of eosinophils and platelets in the airways; suppression of the priming of eosinophils by human recombinant cytokines and thereby suppression of the influx of eosinophils into inflammatory loci; antagonism of bronchoconstriction due to leukotrienes. In Vitro results: inhibition of the release of allergic mediators such as histamine, leukotrienes C4 and D4 (SRS-A) and PAF. /Ketotifen fumarate (systemic)/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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. ...

/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.

4,9-Dihydro-4-(1-methyl-4-piperidylidene)-10H-benzo(4,5)-cyclohepta(1,2-b)thiophen-10-one

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/

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals