Ketotifen Description

Ketotifen is an antihistamine drug that is used for the treatment of general allergy symptoms, certain allergic conditions (including conjunctivitis), and the management of asthma. When used for asthma, the drug is not regarded as effective for treating an immediate attack (it is not a rapid bronchodilator). Instead, over time its use is associated with a reduction in the frequency, duration, and severity of attacks. It is usually prescribed as a way to increase the efficacy of other asthma medications. Likewise, ketotifen fumarate will usually supplement an existing asthma medication program, and not replace the prescribing of immediate rescue devices such as an asthma inhaler or nebulizer.

Ketotifen fumarate alleviates allergy symptoms by blocking histamine H1 receptors, a property that is common to drugs of the antihistamine class. Its second and very unique mode of action, however, makes it useful in the treatment of asthma. Ketotifen fumarate increases the concentration of beta-adrenergic receptors in the body (especially beta-2 receptors). Drugs that stimulate beta-2 receptors are commonly prescribed as bronchodilators, used to increase airflow to the lungs and counter the constriction caused by asthma. While potentially efficacious alone, one key therapeutic effect of ketotifen fumarate is to increase the sensitivity of the body to drugs of the beta-agonist class.

The beta-2 receptor upregulating properties of ketotifen fumarate make this drug of interest to the bodybuilding and athletic communities. This is due to the strong role of the beta-2 receptor in supporting fat loss. Although not a strong fat loss compound by itself, when taken with a beta-2 agonist thermogenic like clenbuterol, ketotifen fumarate may increase thermogenic potency and noticeably extend the window of active lipolysis. Clenbuterol and other beta-2 agonists normally have a limited duration of usefulness here because beta-2-adrenergic receptors decrease in number with regular stimulation. Within several weeks of initiating therapy with such a drug, it usually begins to diminish ineffectiveness. Ketotifen may extend this time period considerably.

The ability of ketotifen to potentiate the effects of beta-2 agonist drugs has been demonstrated in a number of clinical studies. For example, one study published in 1990 demonstrated that when ketotifen and clenbuterol were taken together, there was a significant increase in betaa-drenergic receptor density compared to the use of clenbuterol alone, which again decreases beta-adrenoceptor density fairly quickly.¹ Other studies with salbutamol (also referred to generically as albuterol) showed that beta-adrenoceptor downregulation caused by long-term use of this beta-adrenergic agent could be rapidly reversed with as little as 2mg of ketotifen fumarate per day.²

History

Ketotifen was globalized as a prescription medication by Novartis. It is presently prescribed for allergies, allergic conditions, and (most commonly) the management of asthma in more than three-dozen countries around the world. The most widely available brand name is Novartis’ Zaditen, which is sold throughout most parts of Europe and Asia. In addition to generic forms of the medication, dozens of other brand names can be found in many different markets as well. Ketotifen fumarate is approved for sale in the United States, but currently only as an ophthalmic anti-allergy solution (Zaditor), not an oral allergy/asthma medication. The dosage of ketotifen fumarate in this product is also too low for it to be considered useful for any other (off label) purpose. Given the ready availability of ketotifen fumarate in other countries, the drug is easily diverted for black market sales. As of now, it is not extremely popular with bodybuilders and athletes.

The UK guidelines on the clinical management of asthma consider ketotifen to be ineffective for the management of this disease. There is admittedly conflicting data on the potential usefulness of ketotifen fumarate for this purpose, with some studies reporting positive results and others showing an insignificant effect. A thorough review of the data published on the Cochrane Database of Systematic Reviews in 2004 concluded that it appeared to have some usefulness in controlling asthma and wheezing in many children, but the variability of the disease and response to the drug meant that these positive results could not be generalized for all asthma patients.³

How Supplied

Ketotifen fumarate is most commonly supplied in tablets of 1mg. This dosage is usually expressed in terms of the base, so each tablet actually contains 1.38mg of ketotifen fumarate.

Structural Characteristic

Ketotifen fumarate is a selective histamine H1 antagonist, anti-allergic, and anti-asthmatic agent. It has the chemical designation 4-(1-Methyl-4-piperidylidene-4Hbenzo [4,5]cyclohepta[1,2-b]thiphene-1-(9H)-one fumarate.

Side Effects

Common side effects include dry mouth, appetite stimulation, weight gain, dizziness, CNS stimulation, and drowsiness. These side effects are all commonly associated with strong antihistamine compounds. In rare cases, severe allergic reaction on the skin or a urinary bladder inflammation called cystitis may occur.

Administration

When used to reduce the frequency, duration, and severity of asthma attacks, ketotifen fumarate is usually initiated at a dosage of 1mg twice per day (2mg total). If necessary, this may be increased to a maximum dosage of 2mg twice per day (4mg total). Bodybuilders and athletes will commonly use a dosage of 1mg twice per day (2mg total) for the (off-label) use of preventing receptor downregulation with clenbuterol or other beta-agonists. This may allow an individual to obtain a strong thermogenic effect from, and run longer cycles with, beta-2 agonist drugs. Note that given its ability to increase drug sensitivity, the dosage of beta-2 agonist medications may need to be reduced upon ketotifen fumarate administration.

Availability

Ketotifen fumarate is widely available and is sold under numerous brand names in many countries. Large scale counterfeiting of this medication is currently not known to be a problem.

References:

1. ¹ Effects of ketotifen and clenbuterol on beta-adrenergic receptor functions of lymphocytes and on plasma TXB-2 levels of asthmatic patients. Huszar E, Herjavecz I et al. Z Erkr Atmungsorgane 1990;175(3):141-6
2. ² Effect of prednisolone and ketotifen on beta 2-adrenoceptors in asthmatic patients receiving beta 2-bronchodilators. Brodde OE, Howe U et al. Eur J Clin Pharmacol 1988;34(2):145-50
3. ³ Ketotifen alone or as an additional medication for the long-term control of asthma and wheeze in children. Bassler D, et al. The Cochrane Database of Systematic Reviews; Issue 1. Chichester: John Wiley; 2004.