Ketotifen (Zatofen, Zaditen) is a second-generation antihistamine with mast-cell stabilizing activity. It is used for the prophylactic treatment of children with atopic asthma.
Ketotifen Uses:
-
Atopic asthma:
- Adjunctive treatment in the chronic mild, atopic asthma in children.
- Limitations of use: Not indicated for severe prevention or treatment of severe asthma attacks.
Read:
Ketotifen (Zatofen) dose in Adults:
It can be taken twice daily as 1 mg pills. Upgrading the dosage to 2 mg twice daily is possible.
Ketotifen (Zatofen) Dose in Children:
Ketotifen (Zatofen) Dose for prophylaxis in patients with Atopic asthma: Oral:
-
Infants and Children 6 months to 3 years:
- Initial: 0.05 mg/kg one time a day or in 2 divided doses for 5 days;
- The maintenance dose is 0.05 mg/kg/dose two times a day.
- The maximum dose is 1 mg twice daily.
-
Children >3 years and Adolescents:
- Initial: 1 mg one time a day or in 2 divided doses for 5 days;
- The maintenance dose is 1 mg two times a day.
Pregnancy Risk Category: C
- Adverse incidents have been seen in some animal studies.
Use during breastfeeding:
- Breast-feeding is not advised by the manufacturer.
Dose in Kidney Disease:
There is no dosage changes recommended in the manufacturer's labeling.
Dose in Liver disease:
There no dosage changes recommended in the manufacturer's labeling.
Side Effects of Ketotifen (Zatofen):
-
Central Nervous System:
- Disturbed Sleep
- Headache
-
Dermatologic:
- Skin Rash
- Urticaria
-
Endocrine & Metabolic:
- Weight Gain
-
Gastrointestinal:
- Abdominal Pain
- Increased Appetite
-
Infection:
- Influenza
-
Ophthalmic:
- Eyelid Edema
-
Respiratory:
- Respiratory Tract Infection
- Epistaxis
Contraindications to Ketotifen (Zatofen):
- Sensitivity of ketotifen and any other component of the formulation
- Patients allergic to benzoate elements can use ketotifen syrup.
Warnings and precautions
-
Sedation
- Lethargy may result from early treatment. Start your treatment with half of the regular dosage.
- After five days, gradually increase it until you reach the maintenance dose.
- Patients should be aware that some activities require mental attention. (eg. driving or operating machinery).
-
Thrombocytopenia:
- Patients who have taken oral ketotifen in combination with oral antidiabetic drugs have had rare cases of thrombocytopenia.
- Although the manufacturer labeling doesn't specify any associated agents, it recommends that patients receiving parallel treatment have their platelet count checked.
-
Epilepsy:
- It should be used with caution in epileptic patients. It can lower the seizure threshold.
- Rarely have seizures been reported during treatment.
Ketotifen (systemic): Drug Interaction
Risk Factor C (Monitor therapy) |
|
Acetylcholinesterase Inhibitors |
May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. |
Alcohol (Ethyl) |
Alcohol's CNS depressing effect may be amplified by CNS depressants (Ethyl). |
Alizapride |
CNS depressants may have an enhanced CNS depressant impact. |
Amantadine |
May strengthen an anticholinergic agent's anticholinergic action. |
Amezinium |
Antihistamines may intensify Amezinium's stimulant effects. |
Amphetamines |
May lessen antihistamines' sedative effects. |
Anticholinergic Agents |
Other anticholinergic agents' negative or hazardous effects might be amplified. |
Betahistine |
Antihistamines may diminish the therapeutic effect of Betahistine. |
Botulinum Toxin-Containing Products |
May enhance the anticholinergic effect of Anticholinergic Agents. |
Brexanolone |
CNS Depressants may enhance the CNS depressant effect of Brexanolone. |
Brimonidine (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
Bromopride |
May enhance the CNS depressant effect of CNS Depressants. |
Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
Cannabis |
May enhance the CNS depressant effect of CNS Depressants. |
Chloral Betaine |
May enhance the adverse/toxic effect of Anticholinergic Agents. |
Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of CNS Depressants. |
CNS Depressants |
CNS depressants may have an enhanced CNS depressant impact. |
Dimethindene (Topical) |
CNS depressants may have an enhanced CNS depressant impact. |
Doxylamine |
CNS depressants may have an enhanced CNS depressant impact. Management: The producer of the pregnancy-safe drug Diclegis (doxylamine/pyridoxine) particularly advises against combining it with other CNS depressants. |
Dronabinol |
.CNS depressants may have an enhanced CNS depressant impact. |
Esketamine |
CNS depressants may have an enhanced CNS depressant impact. |
Gastrointestinal Agents (Prokinetic) |
Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). |
Glucagon |
Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. |
HydrOXYzine |
May enhance the CNS depressant effect of CNS Depressants. |
Itopride |
Anticholinergic Agents may diminish the therapeutic effect of Itopride. |
Kava Kava |
CNS depressants may have an enhanced CNS depressant impact. |
Lofexidine |
CNS depressants may have an enhanced CNS depressant impact. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book. |
Magnesium Sulfate |
CNS depressants may have an enhanced CNS depressant impact. |
MetyroSINE |
The sedative effects of metyroSINE may be strengthened by CNS depressants. |
Mianserin |
May strengthen an anticholinergic agent's anticholinergic action. |
Minocycline (Systemic) |
CNS depressants may have an enhanced CNS depressant impact. |
Mirabegron |
Anticholinergic drugs may make Mirabegron's harmful or hazardous effects worse. |
Nabilone |
CNS depressants may have an enhanced CNS depressant impact. |
Nitroglycerin |
Nitroglycerin absorption may be decreased by anticholinergic agents. Anticholinergic medications specifically have the potential to impede or prevent the absorption of nitroglycerin by reducing the breakdown of sublingual nitroglycerin pills. |
Piribedil |
CNS Depressants may enhance the CNS depressant effect of Piribedil. |
Pramipexole |
CNS Depressants may enhance the sedative effect of Pramipexole. |
Ramosetron |
Anticholinergic Agents may enhance the constipating effect of Ramosetron. |
ROPINIRole |
The sedative effects of CNS depressants may increase those of ROPINIRole. |
Rotigotine |
Rotigotine's sedative effects may be boosted by CNS depressants. |
Rufinamide |
CNS depressants' harmful or toxic effects could be increased. Particularly, drowsiness and lightheadedness could be worsened. |
Selective Serotonin Reuptake Inhibitors |
Selective serotonin reuptake inhibitors may have a worsened or more hazardous effect when taken with CNS depressants. Particularly, there may be an increased risk of psychomotor impairment. |
Tetrahydrocannabinol |
May enhance the CNS depressant effect of CNS Depressants. |
Tetrahydrocannabinol and Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
Thiazide and Thiazide-Like Diuretics |
Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. |
Topiramate |
Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. |
Trimeprazine |
May enhance the CNS depressant effect of CNS Depressants. |
Risk Factor D (Consider therapy modification) |
|
Benzylpenicilloyl Polylysine |
Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. |
Blonanserin |
CNS Depressants may enhance the CNS depressant effect of Blonanserin. |
Buprenorphine |
The CNS depressing impact of buprenorphine may be enhanced by CNS depressants. Treatment: If a patient has a high risk of abusing or injecting themselves with buprenorphine, consider reducing the doses of other CNS depressants and avoiding such medications. Buprenorphine should be started at lower doses in individuals who are currently taking CNS depressants. |
Chlormethiazole |
May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. |
Droperidol |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
Flunitrazepam |
CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. |
Hyaluronidase |
Antihistamines may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. |
HYDROcodone |
CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
Lemborexant |
CNS depressants may have an enhanced CNS depressant impact. Management: Due to the possibility of additive CNS depressant effects when lemborexant and concurrent CNS depressants are administered concurrently, dosage modifications may be required. Effects of CNS depressants must be closely monitored. |
Methotrimeprazine |
The CNS depressing action of methotrimeprazine may be enhanced by CNS depressants. The CNS depressant action of CNS Depressants may be strengthened by methotrimeprazine. Management: Start concurrent methotrimeprazine therapy while reducing the adult dose of CNS depressants by 50%. Only once a clinically effective dose of methotrimeprazine has been established should additional CNS depressant dosage modifications be made. |
Opioid Agonists |
CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
OxyCODONE |
CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
Perampanel |
May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. |
Pramlintide |
May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. |
Secretin |
Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. |
Sodium Oxybate |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. |
Suvorexant |
CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. |
Tapentadol |
May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
Zolpidem |
CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. |
Risk Factor X (Avoid combination) |
|
Aclidinium |
May enhance the anticholinergic effect of Anticholinergic Agents. |
Azelastine (Nasal) |
CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). |
Bromperidol |
May enhance the CNS depressant effect of CNS Depressants. |
Cimetropium |
Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. |
Eluxadoline |
Anticholinergic Agents may enhance the constipating effect of Eluxadoline. |
Glycopyrrolate (Oral Inhalation) |
Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). |
Glycopyrronium (Topical) |
May enhance the anticholinergic effect of Anticholinergic Agents. |
Ipratropium (Oral Inhalation) |
May enhance the anticholinergic effect of Anticholinergic Agents. |
Levosulpiride |
Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. |
Orphenadrine |
CNS Depressants may enhance the CNS depressant effect of Orphenadrine. |
Oxatomide |
May strengthen an anticholinergic agent's anticholinergic action. |
Oxomemazine |
CNS depressants may have an enhanced CNS depressant impact. |
Paraldehyde |
The CNS depressing effects of paraldehyde may be enhanced by CNS depressants. |
Pitolisant |
Pitolisant's therapeutic effects may be lessened by antihistamines. |
Potassium Chloride |
Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. |
Potassium Citrate |
Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. |
Revefenacin |
Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. |
Thalidomide |
CNS Depressants may enhance the CNS depressant effect of Thalidomide. |
Tiotropium |
Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. |
Umeclidinium |
May enhance the anticholinergic effect of Anticholinergic Agents. |
Monitoring parameters:
Manufacturer labeling suggests checking platelet counts in patients getting oral antidiabetic agents.
How to administer Ketotifen (Zatofen)?
Oral: Administer without regard to meals.
Syrup: Use the measuring device that comes with this drug or a calibrated measuring device.
Mechanism of action of Ketotifen (Zatofen):
- It has noncompetitive H-1 receptor antagonist properties and mast cell stabilizer properties.
- The drug's effectiveness in asthma is likely due to a combination anti-inflammatory and antihistaminic activities, including inhibition of platelet activating factor (PAF)-induced hyperreactivity and interference with chemokine induced migration of eosinophils in inflamed airways.
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:
- About 50%
Half-life elimination:
- Biphasic: Distribution: 3 to 5 hours;
- Elimination: 21 hours
Time to peak, plasma:
- 2 to 4 hours
Excretion:
- Urine (>60% as metabolites, 1% as unchanged drug)
International Brand Names of Ketotifen:
- APO-Ketotifen
- Zaditen
- Allerban
- Allerfen
- Amitone
- Asmafort
- Asmaten
- Asthafen
- Asthan
- Asumalife
- Azimet
- Bronket
- Butifeno
- Denerel
- Dhatifen
- Edifen
- Eucycline
- Gloditen
- Ketasma
- Ketifen
- Keto
- Ketof
- Ketohexal
- Ketokid
- Ketomin
- Ketop
- Ketosma
- Ketotisin
- Ketovent
- Orpidix
- Politifen
- Profilar
- Profiten
- Prophallerge
- Prosma 1
- Rui Na Ti
- Santiten
- Soother
- Stafen
- Sykofen
- Tefanyl
- Tokn
- Tosma
- Totinal
- Zadec
- Zadec SRO
- Zadin
- Zaditen
- Zaditen SDU
- Zasten
- Zatin
- Zatofen
- Zerosma
- Zylofen
- Zytofen
Ketotifen Brand Names in Pakistan:
Ketotifen Fumarate Eye Drops 0.69 mg/ml in Pakistan |
|
Ketolerg | Global Pharmaceuticals |
Zaditen | Novartis Pharma (Pak) Ltd |
Ketotifen Fumarate Eye Drops 0.345 Mg/Ml in Pakistan |
|
Deketofin | Shaigan Pharmaceuticals (Pvt) Ltd |
Ketotifen Fumarate Syrup 1 Mg/5ml in Pakistan |
|
Aria | Highnoon Laboratories Ltd. |
Asfen | Remington Pharmaceutical Industries (Pvt) Ltd. |
Asmarax | Mediceena Pharma (Pvt) Ltd. |
Asmofen | Medicaids Pakistan (Pvt) Ltd. |
Asperfin | Davis Pharmaceutical Laboratories |
Asthacure | Medicraft Pharmaceuticals (Pvt) Ltd. |
Asthama | Olive Laboratories |
Asthanil | Siza International (Pvt) Ltd. |
Asthotifen | Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
Bronclear | Neo Medix |
Deasma | Rakaposhi Pharmaceutical (Pvt) Ltd. |
Gratifen | Gray`S Pharmaceuticals |
Katifen | Pakistan Pharmaceutical Products (Pvt) Ltd. |
Keften | Helicon Pharmaceutek Pakistan (Pvt) Ltd. |
Ketozad | Dosaco Laboratories |
Kotin | Schazoo Zaka |
Mactifen | Macter International (Pvt) Ltd. |
Naveten | Navegal Laboratories |
Proasma | Platinum Pharmaceuticals (Pvt.) Ltd. |
Tifen | Alina Combine Pharmaceuticals (Pvt) Ltd. |
Totifen | Lahore Chemical & Pharmaceutical Works (Pvt) Ltd |
Zag | Libra Pharmaceuticals (Pvt) Ltd |
Zatofen | Novartis Pharma (Pak) Ltd |
Ketotifen Fumarate Syrup 0.2 Mg/Ml in Pakistan |
|
Bronk | Semos Pharmaceuticals (Pvt) Ltd. |
Zofen | Jawa Pharmaceuticals(Pvt) Ltd. |
Ketotifen Fumarate Syrup 0.2 Mg/5ml in Pakistan |
|
Asthonex | Medera Pharmaceuticals (Pvt) Ltd. |
Zatox | Neo Medix |
Ketotifen Fumarate Tablets 1 Mg in Pakistan |
|
Aria | Highnoon Laboratories Ltd. |
Asfen | Remington Pharmaceutical Industries (Pvt) Ltd. |
Asmarax | Mediceena Pharma (Pvt) Ltd. |
Asmofen | Medicaids Pakistan (Pvt) Ltd. |
Asperfin | Davis Pharmaceutical Laboratories |
Asthacure | Medicraft Pharmaceuticals (Pvt) Ltd. |
Asthanil | Siza International (Pvt) Ltd. |
Asthonex | Medera Pharmaceuticals (Pvt) Ltd. |
Asthotifen | Zafa Pharmaceutical Laboratories (Pvt) Ltd. |
Bronk | Semos Pharmaceuticals (Pvt) Ltd. |
Gratifen | Gray`S Pharmaceuticals |
Keften | Helicon Pharmaceutek Pakistan (Pvt) Ltd. |
Ketofen | Karachi Chemical Industries |
Kotin | Schazoo Zaka |
Maktofen | Makson Pharmaceuticals |
Naveten | Navegal Laboratories |
Proasma | Platinum Pharmaceuticals (Pvt.) Ltd. |
Tifen | Alina Combine Pharmaceuticals (Pvt) Ltd. |
Zag | Libra Pharmaceuticals (Pvt) Ltd |
Zatofen | Novartis Pharma (Pak) Ltd |
Zatox | Neo Medix |
Zofen | Jawa Pharmaceuticals(Pvt) Ltd. |
Ketotifen Fumarate Capsules 1 Mg in Pakistan |
|
Katifen | Pakistan Pharmaceutical Products (Pvt) Ltd. |
Mactifen | Macter International (Pvt) Ltd. |
Totifen | Lahore Chemical & Pharmaceutical Works (Pvt) Ltd |