Ketotifen (Zatofen, Zaditen) - Uses, Dose, MOA, Brands, Side effects

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