|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
Claritin™ Eye (ketotifen) may be confused with Claritin® (loratadine)
Ketotifen may be confused with ketoprofen
Zyrtec® Itchy Eye (ketotifen) may be confused with Zyrtec® (cetirizine)
Pronunciation
(kee toe TYE fen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Ophthalmic: Temporary relief of eye itching due to allergic conjunctivitis
Oral (Canadian use; not approved in U.S.): Adjunctive therapy in the chronic treatment of pediatric patients ?6 months of age with mild, atopic asthma
Restrictions
Oral formulation not available in U.S.
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse fetal effects were found in some but not all animal studies. Topical ocular administration has not been studied.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to ketotifen or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Sedation (oral use): May cause drowsiness early in therapy; initiate therapy at one-half the recommended daily dose and gradually increase over 5 days to maintenance dose; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Thrombocytopenia: Rare cases of thrombocytopenia have been reported in patients concurrently using oral ketotifen and oral antidiabetic agents.
Concurrent drug therapy issues:
• Antiasthmatic agents: Oral ketotifen should not be used to treat acute asthma attacks. Therapy with agents used for prophylaxis or relief of asthma related symptoms (eg, corticosteroids, beta2-agonists, xanthine derivatives), should be not be interrupted nor should dosing be immediately reduced with the onset of ketotifen therapy. Reduce dosing gradually especially in patients taking corticosteroids or ACTH therapy. Steroid-dependent patients with adrenocortical insufficiency can take up to one year to recover a normal stress related pituitary-adrenal response.
Special populations:
• Contact lens wearers: Ophthalmic solution: Not to treat contact lens-related irritation. After ketotifen use, soft contact lens wearers should wait at least 10 minutes before putting their lenses in. Do not wear contact lenses if eyes are red. Do not contaminate dropper tip or solution when placing drops in eyes.
• Diabetics: Due to the carbohydrate content of the syrup preparation, diabetic patients may need to use alternative dosage form (tablet)
• Pediatrics: Safety and efficacy have not been established in children <3 years of age for ophthalmic preparations or <6 months of age for oral preparations.
Dosage form specific issues:
• Benzoate allergy: Syrup products may contain benzoate compounds.
Other warnings/precautions:
• Delayed clinical response: Therapeutic effects may not be clinically evident until several weeks after the initiation of therapy while full effectiveness is usually not evident until after 10 weeks of therapy. Patients with an inadequate response after a few weeks should be maintained for at least 2-3 months on therapy. Discontinuation of therapy if needed should occur gradually over 2-4 weeks however symptoms of asthma may reoccur with discontinuation.
• Self-medication (OTC use): ophthalmic solution: When used for self-medication (OTC), notify healthcare provider if symptoms worsen or do not improve within 3 days. Contact healthcare provider if change in vision, eye pain, or redness occur. Do not use, if solution is cloudy or changes color. Not for OTC use in children <3 years of age.
Adverse Reactions
Ophthalmic: 1% to 10%:
Ocular: Allergic reactions, burning or stinging, conjunctivitis, discharge, dry eyes, eye pain, eyelid disorder, itching, keratitis, lacrimation disorder, mydriasis, photophobia, rash
Respiratory: Pharyngitis
Miscellaneous: Flu syndrome
Oral:
1% to 10%:
Central nervous system: Sedation (8%; less than placebo), headache (1%), sleep disturbance (1%)
Dermatologic: Rash (4%), urticaria (1%)
Gastrointestinal: Weight gain (5%), abdominal pain (1%), appetite increased (1%)
Respiratory: Respiratory infection (4%), epistaxis (1%)
Miscellaneous: Flu (3%), puffy eyelid (1%)
<1%, postmarketing, and/or case reports: Cystitis, dizziness, erythema multiforme, excitation, insomnia, irritability, nervousness, Stevens-Johnson syndrome, thrombocytopenia, transaminases increased, xerostomia
Drug Interactions
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Olopatadine, Ophthalmic. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Effects may be increased with concomitant use of ketotifen.
Storage
Ophthalmic solution: Store at 20°C to 25°C (68°F to 77°F).
Syrup: Store at up to 25°C (up to 77°F).
Tablet: Store at 15°C to 25°C (59°F to 77°F).
Mechanism of Action
Exhibits noncompetitive H1-receptor antagonist and mast cell stabilizer properties. Efficacy in conjunctivitis and asthma likely results from a combination of anti-inflammatory and antihistaminergic actions including interference with chemokine-induced migration of eosinophils into inflamed conjunctiva and airways, inhibition of airway hyper-reactivity due to platelet activating factor (PAF), antagonism of leukotriene-induced bronchoconstriction.
Pharmacodynamics/Kinetics
Ophthalmic:
Onset of action: Minutes
Duration: 8-12 hours
Absorption: Minimally systemic
Oral:
Absorption: Rapid, ?60%
Protein binding: 75%
Metabolism: Hepatic via N-glucuronidation to inactive metabolite ketotifen-N-glucoronide; N-demethylation to active metabolite nor-ketotifen; and keto-reduction to hydroxyl derivative
Clearance: Increased in children >3 years; decreased in children ?3 years
Bioavailability: ~50%
Half-life elimination: ~9-9.5 hours
Time to peak, plasma: 2-4 hours
Excretion: Urine (60% to 70% as metabolites, 1% as unchanged drug)
Dosage
Ophthalmic: Allergic conjunctivitis: Children ?3 years and Adults: Instill 1 drop into the affected eye(s) twice daily, every 8-12 hours
Oral (not approved in U.S.): Atopic asthma (Note: Not for acute attacks):
Children 6 months to 3 years: Initial: 0.025 mg/kg once daily or in 2 divided doses for 5 days; Maintenance: 0.05 mg/kg twice daily
Children >3 years: Initial: 0.5 mg once daily or in 2 divided doses for 5 days; Maintenance: 1 mg twice daily
Administration: Oral
May administer without regard to meals.
Dietary Considerations
Novo-Ketotifen® syrup contains carbohydrate 4 g/5 mL.
Patient Education
Ophthalmic use: For use in eyes only. Do not let tip of applicator touch eye; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Not to be used to treat contact lens-related irritation. Wait at least 10 minutes before putting soft contact lenses in. Do not wear contact lenses if eyes are red.
Oral: Do not use to treat acute asthmatic attacks. Therapeutic effects may not be clinically evident until several weeks after the initiation of therapy. Do not discontinue abruptly. You may experience drowsiness or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known).
Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant or breast-feeding.
Geriatric Considerations
Instruct the patient on proper instillation of ophthalmic solution.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Pharyngitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May cause dry eyes which can be exacerbated by anticholinergic agents or psychotropics with significant anticholinergic activity
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Assess therapeutic response and adverse effects. Teach patient proper use, side effects/appropriate interventions, and symptoms to report. Taper dosage slowly when discontinuing. Do not discontinue abruptly.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Solution, ophthalmic [drops]: 0.025% (5 mL)
Alaway™: 0.025% (10 mL) [contains benzalkonium chloride]
Claritin™ Eye: 0.025% (5 mL) [contains benzalkonium chloride]
Zaditor®: 0.025% (5 mL) [contains benzalkonium chloride]
Zyrtec® Itchy Eye: 0.025% (5 mL) [contains benzalkonium chloride]
Syrup: 1 mg/5 mL (250 mL) [not available in U.S.]
Novo-Ketotifen® [CAN]: 1 mg/5 mL (250 mL) [not available in U.S.; contains alcohol, benzoate compounds; strawberry flavor]
Nu-Ketotifen® [CAN]: 1 mg/5 mL (250 mL) [not available in U.S.]
Zaditen® [CAN]: 1 mg/5 mL (250 mL) [not available in U.S.]
Tablet: 1 mg [not available in U.S.]
Novo-Ketotifen® [CAN]: 1 mg [not available in U.S.]
Zaditen® [CAN]: 1 mg [not available in U.S.]
Pricing: U.S. (www.drugstore.com)
Solution (Zaditor)
0.025% (5): $69.99
References
Hung CH, Li CY, Lai YS, et al, “Discrepant Clinical Responses and Blood Chemokine Profiles Between Two Non-Steroidal Anti-Inflammatory Medications for Children With Mild Persistent Asthma,” Pediatr Allergy Immunol, 2005, 16(4):306-9.
Kabra SK, Pandey RM, Singh R, et al, “Ketotifen for Asthma in Children Aged 5 to 15 Years: A Randomized Placebo-Controlled Trial,” Ann Allergy Asthma Immunol, 2000. 85(1):46-52.
Woerly G, Loiseau S, Loyens M, et al, “Inhibitory Effects of Ketotifen on Eotaxin-Dependent Activation of Eosinophils: Consequences for Allergic Eye Diseases,” Allergy, 2003, 58(5): 397-406.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2010
Content last modified January 2010
| 
