Dolutegravir/phenobarbital interaction

Dolutegravir/phenobarbital interaction Reactions 1704, p143 - 2 Jun 2018 Decreased dolutegravir concentration: case report A 41-year-old man showed decreased plasma concentration of dolutegravir following concomitant administration of dolutegravir and phenobarbital [routes not stated]. The man, who had HIV infection, started receiving combination antiretroviral treatment (cART) with dolutegravir 50mg daily with concomitant tenofovir disoproxil fumarate/ emtricitabine. He had been taking phenobarbital 40mg daily as hypnotic along with various other drugs. The dolutegravir and phenobarbital were administered at bedtime at more than 3 4 hours after dinner. He complained of nocturnal awakening. Therefore, flunitrazepam was replaced with nitrazepam at cART day 140. On day 168 of the start of cART, due to insufficient sleep, nitrazepam was discontinued and the dose of phenobarbital was increased 70mg daily along with chlorpromazine and promethazine. His sleep disturbance continued and a potential drug-drug interaction between dolutegravir and phenobarbital was considered. Therefore, the man’s dose of chlorpromazine, promethazine and phenobarbital were reduced to 25mg, 12.5mg and 40mg daily. On day 196 of the start of cART, suvorexant was added to the treatment. On day 224 of the start of cART, the doses of chlorpromazine and phenobarbital were further reduced to 12.5mg and 30mg daily, respectively to improve the quality of sleep, while clonazepam was added to the treatment. On day 252 of the start of cART, chlorpromazine, promethazine and phenobarbital were stopped and clonazepam dose was increased. The liquid chromatography-mass spectrometry showed dolutegravir plasma concentrations of 0.934 µg/mL at 13 hours after last administration, 1.321 µg/mL at 9 hours after last administration, 0.584 µg/mL at 12 hours after last administration, 1.003 µg/mL at 12 hours after last administration and 3.25 µg/mL at 12 hours after last administration with corresponding phenobarbital doses of 40mg, 40mg, 70mg, 30mg and 0mg daily, respectively. It was considered that, the drug-drug interaction between dolutegravir and phenobarbital led to decreased plasma concentration of dolutegravir. Author comment: "This case suggests that [phenobarbital] can lead to a remarkable reduction in the plasma concentration of [dolutegravir] in a dose-dependent manner." "[A] potential drug-drug interaction between [phenobarbital] and [dolutegravir] was considered". "In conclusion, [phenobarbital] can remarkably decrease the plasma concentrations of [dolutegravir] in a dose-dependent manner." Hikasa S, et al. A potential drug interaction between phenobarbital and dolutegravir: A case report. Journal of Infection and Chemotherapy 24: 476-478, No. 6, Jun 2018. Available from: URL: http://doi.org/10.1016/j.jiac.2017.12.022 - Japan 803322990 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reactions Weekly Springer Journals

Dolutegravir/phenobarbital interaction

Reactions Weekly , Volume 1704 (1) – Jun 2, 2018
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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer International Publishing AG, part of Springer Nature
Subject
Medicine & Public Health; Drug Safety and Pharmacovigilance; Pharmacology/Toxicology
ISSN
0114-9954
eISSN
1179-2051
D.O.I.
10.1007/s40278-018-46786-2
Publisher site
See Article on Publisher Site

Abstract

Reactions 1704, p143 - 2 Jun 2018 Decreased dolutegravir concentration: case report A 41-year-old man showed decreased plasma concentration of dolutegravir following concomitant administration of dolutegravir and phenobarbital [routes not stated]. The man, who had HIV infection, started receiving combination antiretroviral treatment (cART) with dolutegravir 50mg daily with concomitant tenofovir disoproxil fumarate/ emtricitabine. He had been taking phenobarbital 40mg daily as hypnotic along with various other drugs. The dolutegravir and phenobarbital were administered at bedtime at more than 3 4 hours after dinner. He complained of nocturnal awakening. Therefore, flunitrazepam was replaced with nitrazepam at cART day 140. On day 168 of the start of cART, due to insufficient sleep, nitrazepam was discontinued and the dose of phenobarbital was increased 70mg daily along with chlorpromazine and promethazine. His sleep disturbance continued and a potential drug-drug interaction between dolutegravir and phenobarbital was considered. Therefore, the man’s dose of chlorpromazine, promethazine and phenobarbital were reduced to 25mg, 12.5mg and 40mg daily. On day 196 of the start of cART, suvorexant was added to the treatment. On day 224 of the start of cART, the doses of chlorpromazine and phenobarbital were further reduced to 12.5mg and 30mg daily, respectively to improve the quality of sleep, while clonazepam was added to the treatment. On day 252 of the start of cART, chlorpromazine, promethazine and phenobarbital were stopped and clonazepam dose was increased. The liquid chromatography-mass spectrometry showed dolutegravir plasma concentrations of 0.934 µg/mL at 13 hours after last administration, 1.321 µg/mL at 9 hours after last administration, 0.584 µg/mL at 12 hours after last administration, 1.003 µg/mL at 12 hours after last administration and 3.25 µg/mL at 12 hours after last administration with corresponding phenobarbital doses of 40mg, 40mg, 70mg, 30mg and 0mg daily, respectively. It was considered that, the drug-drug interaction between dolutegravir and phenobarbital led to decreased plasma concentration of dolutegravir. Author comment: "This case suggests that [phenobarbital] can lead to a remarkable reduction in the plasma concentration of [dolutegravir] in a dose-dependent manner." "[A] potential drug-drug interaction between [phenobarbital] and [dolutegravir] was considered". "In conclusion, [phenobarbital] can remarkably decrease the plasma concentrations of [dolutegravir] in a dose-dependent manner." Hikasa S, et al. A potential drug interaction between phenobarbital and dolutegravir: A case report. Journal of Infection and Chemotherapy 24: 476-478, No. 6, Jun 2018. Available from: URL: http://doi.org/10.1016/j.jiac.2017.12.022 - Japan 803322990 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704

Journal

Reactions WeeklySpringer Journals

Published: Jun 2, 2018

References

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