KETOTIFEN FUMARATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Antihistamine and mast cell stabilizer; inhibits release of histamine and other mediators from mast cells; also blocks histamine H1 receptors.
| Metabolism | Hepatic; undergoes glucuronidation and O-demethylation; CYP3A4 minor involvement. |
| Excretion | Renal (50-70% as conjugates, <2% unchanged), fecal (<10%), with enterohepatic circulation. |
| Half-life | Terminal half-life 12-24 hours (mean 18 hours); requires twice-daily dosing after initial titration. |
| Protein binding | ~75%, primarily to albumin. |
| Volume of Distribution | 2.4-3.6 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: ~50% (due to first-pass metabolism); Ophthalmic: minimal systemic absorption (<5%). |
| Onset of Action | Oral: 2-4 weeks for prophylactic effect in asthma; Ophthalmic: 5-15 minutes for histamine-induced effects. |
| Duration of Action | Oral: 8-12 hours (symptom control), requires continuous dosing; Ophthalmic: up to 8 hours for itch relief. |
1 mg orally twice daily; ophthalmic: 1 drop in each eye every 8-12 hours.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment; GFR <30 mL/min: use caution, no specific guidelines. |
| Liver impairment | Child-Pugh Class A and B: no adjustment; Class C: use caution, consider dose reduction due to increased exposure. |
| Pediatric use | Children ≥3 years: 1 mg orally twice daily; <3 years: 0.5 mg twice daily; ophthalmic: 1 drop in each eye every 8-12 hours for children ≥3 years. |
| Geriatric use | Initiate at 0.5 mg twice daily; increase to 1 mg twice daily if tolerated due to increased risk of sedation and dizziness. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects For ophthalmic use only may cause transient stinging.
| Breastfeeding | Ketotifen is excreted into human breast milk; manufacturers report that levels are detectable. The milk-to-plasma (M/P) ratio has not been definitively established in humans, but animal studies indicate excretion. Due to potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Ketotifen fumarate is classified as Pregnancy Category C. In animal studies, ketotifen has been shown to be teratogenic at high doses, causing increased fetal resorption and skeletal abnormalities. However, adequate well-controlled studies in pregnant women are lacking. First trimester exposure: potential risk of fetal harm based on animal data, but human data insufficient; second and third trimester: risk cannot be excluded. Should be used during pregnancy only if the potential benefit outweighs the risk. |
■ FDA Black Box Warning
None.
| Common Effects | Drowsiness |
| Serious Effects |
["Hypersensitivity to ketotifen or any component of the formulation."]
| Precautions | ["Not for treatment of acute symptoms or contact lens-related irritation.","May cause transient stinging or burning upon instillation.","Soft contact lenses should be removed before use and may be reinserted after 10 minutes."] |
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| Fetal Monitoring | Monitor for signs of sedation, dizziness, and anticholinergic effects in the mother. Fetal monitoring: consider periodic ultrasound if used long-term in pregnancy to assess fetal growth and development. No specific fetal monitoring is routinely required, but observe for neonatal adverse effects such as sedation if used near term. |
| Fertility Effects | In animal reproduction studies, ketotifen did not impair fertility at therapeutic doses. However, high doses caused reduced fertility and increased preimplantation loss. Human data on fertility effects are lacking; theoretical risk of hormonal or gamete effects exists due to antihistamine and mast cell stabilizing properties, but no specific studies have been conducted. |