- Email: [email protected]
Antihistamines
Inga Lunde
16 HI-RECEPTOR A N T A G O N I S T S (SED-IO,
284; SEDA-8, 165; SEDA-9, 149) As usual, the number of publications on H 1histamine receptor antagonists continues to be low.
Acrivastine (BW-825C) This new antihistamine has been compared to triprolidine (2.5 and 5mg) in a pharmacodynamic and pharmacokinetic study in healthy volunteers. The 2 compounds were approximately equipotent in blocking the flare and wheal response to intradermal histamine. These very preliminary studies indicate that acrivastine causes less sedation and has less effect on vigilance and reaction time than triprolidine (lC). Obviously, further clinical studies are needed.
Azatadine (SEDA-8, 167; SEDA-9, 149) This antihistamine was compared to terfenadine in a multicenter double-blind trial in patients with chronic urticaria. In the doses used, azatadine was found to be more effective than terfenadine. Seventeen of 27 patients in the azatadine group complained of sedation, compared to 7 of 24 patients in the terfenadine group. The sedation did however persist after withdrawal of the drugs in 5 of the patients from the azatadine group and 1 from the terfenadine group. Dryness of the mouth was observed in 7 patients in the azatadine group and 9 in the terfenadine group. One patient in each treatment group complained of headache. One patient in the terfenadine group reacted with nervousness and anxiety. Withdrawal of treatment because of adverse reactions was necessary in only 1 patient in the terfenadine group because of tiredness (2c). Previous findings concerning terfenadine (see below) make these results difficult to assess since placebo control was not used.
Side Effects of Drugs Annual 10 M.N.G. Dukes, editor 9 Elsevier Science Publishers B.V., 1986
Antihistamines A case of a dystonic reaction to a large overdose of azatadine has been reported. The patient took 20-30 mg of azatadine for a possible hallucinatory effect, and developed intermittent, painless, involuntary neck spasms with difficulty in speaking. Benzatropine was given and the symptoms disappeared after a few minutes (3c).
Doxylamine (SEDA-9, 149) Doxylamine is an antihistamine with sedative properties. Its sedative effect has been compared to placebo in patients with insomnia in a double-blind cross-over trial. Each patient was treated for 1 week with doxylamine and 1 week with placebo. Doxylamine was shown to be more effective for insomnia than placebo. As could be expected, the side effects were more frequently reported by patients taking doxylamine than placebo (4c).
Ketotifen (Zaditen) This drug is reviewed in Chapter 17.
Mequitazine (SED-IO, 287; SEDA-8, 165; SEDA-9, 151) Mequitazine has been compared to terfenadine in patients with allergic rhinitis in a double-blind study involving 127 patients. The treatment period was 7 days. The incidence of side effects was the same in both groups. Drowsiness was noted in 11% of the terfenadine group compared to 15% in the mequitazine group. The other adverse effects noted included headache and palpitation (5c). Previous findings (see below) concerning the sedative effects of terfenadine make it difficult to assess these results since placebo control was not used.
Oxatomide (SED-IO, 287; SEDA-8, 166; SEDA-9, 151) Breast engorgement with galactorrhea occurred in a woman participating in a study of oxatomide in patients with chronic urticaria.
136 The reaction was not confirmed by rechallenge. The other side effects reported were of 'classical' type: increased appetite, somnolence and gastric complaints (6~).
Terfenadine (SED-IO, 288; SEDA-8, 168; SEDA-9, 151)
This relatively new antihistamine is claimed not to penetrate into the central nervous system. An extensive review of experience with the drug in about 2000 patients confirms the earlier impression that the frequency of sedation with this drug is comparable to placebo (7R). The incidence due to terfenadine or placebo ranged from 2.2-20% compared with 18-60% for other traditional antihistamines. Dryness of the mouth occurred in 2 - 5 % of terfenadine-treated patients, 4% of placebo and 3-8% of other patients treated with antihistamines, It would seem that terfenadine offers a worthwhile improvement in the side-effects profile of traditional antihistamines, but more
Chapter 16 L Lunde
experience from wider clinical use is still needed. In this context it should be remembered that it is difficult to define the 'minimum effective dose' for antihistamines. Demonstration of differences in sedation between various antihistamines found in clinical trials may often be explained by the fact that the doses used are not comparable. The studies referred to earlier, where terfenadine is compared to mequitazine (5 c) and azatadine (2c), are not covered in the review article (7R).
Antihistamines and propoxyphene Potentiation of the effect of propoxyphene by antihistamines has been described in 3 patients. These effects included increased analgesia and mild euphoria as well as moderately severe symptoms of opiate withdrawal at therapeutic doses of propoxyphene. Although this interaction clearly needs further investigation, the combination of propoxyphene and antihistamines should probably be avoided (8c).
REFERENCES 1. Cohen AF, Hamilton MJ, Liao SHT et al (1985) Pharmacodynamic and pharmacokinetics of BW, 825C: a new antihistamine. Eur. J. Clin. Pharmacol., 28, 197. 2. Neumann Y (1984) Antihistaminika-Behandlung bei chronischer Urtikaria. Fortschr, Med., 102, 867. 3. Joske DJL (1984) Dystonic reaction to azatadine. Med. J. Austr., 29, 449. 4. Rickels K, Ginsberg J, Morris RJ et al (1984) Doxylamine succinate in insomniac family practice patients: a double blind study. Curr. Ther. Res,, 35, 532. 5. Leophonthe P, Didier A, Leoponthe-Domairon
MLL (1985) Vergelijkend onderzoek van quitazine en terfenadine bij allergische rhinitis. Tijdschr. Ther. Geneesm. Onderz., 10, 573. 6. Valsecchi R, Tribbia G, Frigeni A et al (1984) Impiego dell'oxatomide nella terapia dell'orticaria cronica. Ann. Ital. Dermatol. Clin. Sper., 38, 323. 7. Sorkin EM, Heel RC (1985) Terfenadine: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs, 29, 34. 8. Giannini AJ, Gregg LO, Andriano JP (1984) P's and blue~ potentiation of propoxyphene withdrawal by a variety of antihistamines. Clin. Toxicol., 22, 397.
16 HI-RECEPTOR A N T A G O N I S T S (SED-IO,
284; SEDA-8, 165; SEDA-9, 149) As usual, the number of publications on H 1histamine receptor antagonists continues to be low.
Acrivastine (BW-825C) This new antihistamine has been compared to triprolidine (2.5 and 5mg) in a pharmacodynamic and pharmacokinetic study in healthy volunteers. The 2 compounds were approximately equipotent in blocking the flare and wheal response to intradermal histamine. These very preliminary studies indicate that acrivastine causes less sedation and has less effect on vigilance and reaction time than triprolidine (lC). Obviously, further clinical studies are needed.
Azatadine (SEDA-8, 167; SEDA-9, 149) This antihistamine was compared to terfenadine in a multicenter double-blind trial in patients with chronic urticaria. In the doses used, azatadine was found to be more effective than terfenadine. Seventeen of 27 patients in the azatadine group complained of sedation, compared to 7 of 24 patients in the terfenadine group. The sedation did however persist after withdrawal of the drugs in 5 of the patients from the azatadine group and 1 from the terfenadine group. Dryness of the mouth was observed in 7 patients in the azatadine group and 9 in the terfenadine group. One patient in each treatment group complained of headache. One patient in the terfenadine group reacted with nervousness and anxiety. Withdrawal of treatment because of adverse reactions was necessary in only 1 patient in the terfenadine group because of tiredness (2c). Previous findings concerning terfenadine (see below) make these results difficult to assess since placebo control was not used.
Side Effects of Drugs Annual 10 M.N.G. Dukes, editor 9 Elsevier Science Publishers B.V., 1986
Antihistamines A case of a dystonic reaction to a large overdose of azatadine has been reported. The patient took 20-30 mg of azatadine for a possible hallucinatory effect, and developed intermittent, painless, involuntary neck spasms with difficulty in speaking. Benzatropine was given and the symptoms disappeared after a few minutes (3c).
Doxylamine (SEDA-9, 149) Doxylamine is an antihistamine with sedative properties. Its sedative effect has been compared to placebo in patients with insomnia in a double-blind cross-over trial. Each patient was treated for 1 week with doxylamine and 1 week with placebo. Doxylamine was shown to be more effective for insomnia than placebo. As could be expected, the side effects were more frequently reported by patients taking doxylamine than placebo (4c).
Ketotifen (Zaditen) This drug is reviewed in Chapter 17.
Mequitazine (SED-IO, 287; SEDA-8, 165; SEDA-9, 151) Mequitazine has been compared to terfenadine in patients with allergic rhinitis in a double-blind study involving 127 patients. The treatment period was 7 days. The incidence of side effects was the same in both groups. Drowsiness was noted in 11% of the terfenadine group compared to 15% in the mequitazine group. The other adverse effects noted included headache and palpitation (5c). Previous findings (see below) concerning the sedative effects of terfenadine make it difficult to assess these results since placebo control was not used.
Oxatomide (SED-IO, 287; SEDA-8, 166; SEDA-9, 151) Breast engorgement with galactorrhea occurred in a woman participating in a study of oxatomide in patients with chronic urticaria.
136 The reaction was not confirmed by rechallenge. The other side effects reported were of 'classical' type: increased appetite, somnolence and gastric complaints (6~).
Terfenadine (SED-IO, 288; SEDA-8, 168; SEDA-9, 151)
This relatively new antihistamine is claimed not to penetrate into the central nervous system. An extensive review of experience with the drug in about 2000 patients confirms the earlier impression that the frequency of sedation with this drug is comparable to placebo (7R). The incidence due to terfenadine or placebo ranged from 2.2-20% compared with 18-60% for other traditional antihistamines. Dryness of the mouth occurred in 2 - 5 % of terfenadine-treated patients, 4% of placebo and 3-8% of other patients treated with antihistamines, It would seem that terfenadine offers a worthwhile improvement in the side-effects profile of traditional antihistamines, but more
Chapter 16 L Lunde
experience from wider clinical use is still needed. In this context it should be remembered that it is difficult to define the 'minimum effective dose' for antihistamines. Demonstration of differences in sedation between various antihistamines found in clinical trials may often be explained by the fact that the doses used are not comparable. The studies referred to earlier, where terfenadine is compared to mequitazine (5 c) and azatadine (2c), are not covered in the review article (7R).
Antihistamines and propoxyphene Potentiation of the effect of propoxyphene by antihistamines has been described in 3 patients. These effects included increased analgesia and mild euphoria as well as moderately severe symptoms of opiate withdrawal at therapeutic doses of propoxyphene. Although this interaction clearly needs further investigation, the combination of propoxyphene and antihistamines should probably be avoided (8c).
REFERENCES 1. Cohen AF, Hamilton MJ, Liao SHT et al (1985) Pharmacodynamic and pharmacokinetics of BW, 825C: a new antihistamine. Eur. J. Clin. Pharmacol., 28, 197. 2. Neumann Y (1984) Antihistaminika-Behandlung bei chronischer Urtikaria. Fortschr, Med., 102, 867. 3. Joske DJL (1984) Dystonic reaction to azatadine. Med. J. Austr., 29, 449. 4. Rickels K, Ginsberg J, Morris RJ et al (1984) Doxylamine succinate in insomniac family practice patients: a double blind study. Curr. Ther. Res,, 35, 532. 5. Leophonthe P, Didier A, Leoponthe-Domairon
MLL (1985) Vergelijkend onderzoek van quitazine en terfenadine bij allergische rhinitis. Tijdschr. Ther. Geneesm. Onderz., 10, 573. 6. Valsecchi R, Tribbia G, Frigeni A et al (1984) Impiego dell'oxatomide nella terapia dell'orticaria cronica. Ann. Ital. Dermatol. Clin. Sper., 38, 323. 7. Sorkin EM, Heel RC (1985) Terfenadine: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs, 29, 34. 8. Giannini AJ, Gregg LO, Andriano JP (1984) P's and blue~ potentiation of propoxyphene withdrawal by a variety of antihistamines. Clin. Toxicol., 22, 397.