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Gideon Koren - One of the best experts on this subject based on the ideXlab platform.
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P56 Breakthrough in the treatment of nausea and vomiting of pregnancy; the first dual release combination of Doxylamine-pyridoxine
Archives of Disease in Childhood, 2019Co-Authors: Gideon KorenAbstract:Background Nausea and vomiting of pregnancy (NVP) affect almost pregnancies. The only agent approved by the FDA and other countries for the management of NVP symptoms has been the delayed release combination of Doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed release tablet, was approved by the FDA for the treatment of NVP in 2013 (Diclegis®). Due to its delayed release properties, Diclegis® begins to exert its antiemetic properties 6–8 hours after ingestion, and hence symptom relief may be delayed and necessitate the use of an immediate release medication. Methods In 2016 the FDA approved Bonjesta®, a novel, dual- release combination of Doxylamine and pyridoxine, whereby a rapid release phase is followed by a delayed release phase, thus overcoming the time delay in action of Diclegis®. Bonjesta®, is a multilayer, extended-release tablet consisting of an enteric-coated core containing 10 mg Doxylamine succinate and 10 mg pyridoxine hydrochloride, and an immediate-release coating of 10 mg Doxylamine succinate and 10 mg pyridoxine hydrochloride, delivering a total of 20 mg Doxylamine succinate and 20 mg pyridoxine hydrochloride Results In a single-and multiple dose study in 48 healthy, premenopausal women, one Bonjesta® (20 mg Doxylamine succinate and 20 mg pyridoxine) was bioequivalent to two combination tablets of 10 mg Doxylamine succinate and 10 mg pyridoxine hydrochloride Bonjesta has shown an immediate peak concentrations, followed by a delayed release phase. Conclusions The combination of the immediate release with a delayed action is unique to Bonjesta® as it allows for the bedtime dose to be effective immediately and also provide with sustained control of NVP symptoms throughout the day. Disclosure(s) G Koren has been a consuntant for Duchesnay Inc.
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Treating Symptoms of Morning Sickness: The First Dual Release Combination of Doxylamine-Pyridoxine
2018Co-Authors: Gideon Koren, RickAbstract:Modified release tablet preparations are sought when there is a need to provide clinical solutions which are not achieved optimally with the standard release products. Nausea and vomiting of pregnancy (NVP) affect most pregnancies. Symptomatic treatment aims to improve woman’s quality of life, and counteract dehydration, electrolyte imbalance, need for hospitalization and attendant risk of maternal and fetal complications. Until recently, the only agent approved by Canada, USA, South Korea. Israel and Singapore has been the delayed release combination of Doxylamine and pyridoxine (Diclectin®/ Diclegis®). All other countries worldwide do not presently have a pregnancy- approved anti emetic drug. Due to its delayed release properties, Diclectin®/ Diclegis® begins to exert its antiemetic effect 6-8 hours after ingestion, and hence symptom relief may be delayed and necessitate the use of an immediate release medication. In November 2016 the FDA approved Bonjesta®, a novel, dual- release combination of Doxylamine and pyridoxine, whereby a rapid release phase is followed by a delayed release phase, thus overcoming the time delay in action of the delayed release combination of Doxylamine and pyridoxine. In this article we review the unique properties of this new drug in the context of other medications where modified- release forms have been effective.
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comparing pyridoxine and Doxylamine succinate pyridoxine hcl for nausea and vomiting of pregnancy a matched controlled cohort study
The Journal of Clinical Pharmacology, 2015Co-Authors: Eliza Pope, Caroline Maltepe, Gideon KorenAbstract:Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (Doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or Doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking Doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or Doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where Doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P < .05). As well, Doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores.
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Comparing pyridoxine and Doxylamine succinate‐pyridoxine HCl for nausea and vomiting of pregnancy: A matched, controlled cohort study
Journal of clinical pharmacology, 2015Co-Authors: Eliza Pope, Caroline Maltepe, Gideon KorenAbstract:Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (Doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or Doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking Doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or Doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where Doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P < .05). As well, Doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores.
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Maternal safety of the delayed-release Doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial
BMC pregnancy and childbirth, 2015Co-Authors: Gideon Koren, Shannon Clark, Steve Caritis, Jason Umans, Menachem Miodovnik, Gary D V Hankins, Donald R. Mattison, Ilan MatokAbstract:Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of Doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of Doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo. We randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2–4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing. Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement. Doxylamine succinate–pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy. Clinical Trial Registration No: NCT00614445 .
Yu Wen Chen - One of the best experts on this subject based on the ideXlab platform.
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spinal sensory and motor blockade by intrathecal Doxylamine and triprolidine in rats
Journal of Pharmacy and Pharmacology, 2018Co-Authors: Jann Inn Tzeng, Chong Chi Chiu, Jhijoung Wang, Ching Hsia Hung, Yu Wen ChenAbstract:OBJECTIVES The aim of this experiment was mainly to examine the effects of intrathecally injected Doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions. METHODS After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with Doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with Doxylamine or triprolidine were conducted. KEY FINDINGS Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine > mepivacaine > Doxylamine (P < 0.05) at provoking spinal motor, proprioceptive and nociceptive blockades. On the equianaesthetic doses (ED25 , ED50 and ED75 ), the duration of spinal anaesthesia with Doxylamine was longer (P < 0.01) than that with mepivacaine or triprolidine. Moreover, Doxylamine or triprolidine displayed greater potency (ED50 ) (P < 0.05) and duration (P < 0.05) of sensory block over motor block. CONCLUSIONS Doxylamine or triprolidine produces a dose-dependent effect of spinal motor and sensory block. Triprolidine with a better nociception-selective action over motor block has a better potency than mepivacaine or Doxylamine. Doxylamine and triprolidine produce longer durations than mepivacaine.
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Spinal sensory and motor blockade by intrathecal Doxylamine and triprolidine in rats.
The Journal of pharmacy and pharmacology, 2018Co-Authors: Jann Inn Tzeng, Chong Chi Chiu, Jhijoung Wang, Ching Hsia Hung, Yu Wen ChenAbstract:OBJECTIVES The aim of this experiment was mainly to examine the effects of intrathecally injected Doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions. METHODS After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with Doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with Doxylamine or triprolidine were conducted. KEY FINDINGS Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine > mepivacaine > Doxylamine (P
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Subcutaneous infiltration of Doxylamine on cutaneous analgesia in rats
Pharmacological Reports, 2018Co-Authors: Ching Hsia Hung, Chong Chi Chiu, Jhijoung Wang, Ja-ping Shieh, Yu Wen ChenAbstract:Background We aimed to evaluate the effect of Doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. Methods After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of Doxylamine, we assessed Doxylamine’s cutaneous analgesic effect in rats. The dose-related effect and duration of Doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. Results We demonstrated that Doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED_50)), the relative potency was bupivacaine (0.41 (0.36–0.48) mmol)> Doxylamine (7.39 (6.91–7.91) mmol) ( p < 0.01). On an equipotent basis (ED_25, ED_50 and ED_75), subcutaneous Doxylamine resulted in greater duration of action ( p < 0.01) than bupivacaine at producing cutaneous analgesia. Conclusions The result of this experiment indicated that Doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.
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Subcutaneous infiltration of Doxylamine on cutaneous analgesia in rats.
Pharmacological reports : PR, 2017Co-Authors: Ching Hsia Hung, Chong Chi Chiu, Jhijoung Wang, Ja-ping Shieh, Yu Wen ChenAbstract:Abstract Background We aimed to evaluate the effect of Doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. Methods After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of Doxylamine, we assessed Doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of Doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. Results We demonstrated that Doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36–0.48) mmol)> Doxylamine (7.39 (6.91–7.91) mmol) (p Conclusions The result of this experiment indicated that Doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.
Artur Sans - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetic Dose Proportionality Between Two Strengths (12.5 mg and 25 mg) of Doxylamine Hydrogen Succinate Film-Coated Tablets in Fasting State: A Single-Dose, Randomized, Two-Period Crossover Study in Healthy Volunteers
Drugs in R&D, 2013Co-Authors: Sebastián Videla, Mounia Lahjou, Pascal Guibord, Gregorio Encina, Eric Sicard, Jesús Cebrecos, France Wagner, Anna Cabot, Mercedes Encabo, Artur SansAbstract:Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of Doxylamine are available, although this drug has been marketed in European countries for more than 50 years. Objective The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of Doxylamine hydrogen succinate after a single oral dose administration under fasting conditions in healthy human subjects. Study Design This was a single-center, randomized, single dose, laboratory-blinded, two-period, two-sequence, crossover study. Setting The study was conducted in a phase I clinical unit. Subjects and Methods A single oral dose of Doxylamine hydrogen succinate of 12.5 mg (equivalent to 8.7 mg of Doxylamine base) or 25 mg (equivalent to 17.4 mg of Doxylamine base) was administered to healthy volunteers under fasting conditions in each study period. The drug administrations were separated by a wash-out period of 7 calendar days. Blood samples were collected for up to 60 h post-dose, and plasma Doxylamine levels were determined by an ultra high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using non-compartmental analysis. Dose proportionality was assessed based on the parameter area under the concentration–time curve (AUC_ t normalized). Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs and 12-lead electrocardiogram (ECG). Results In total, 12 healthy volunteers (3 male; 9 female) were included in the study. Mean maximum observed plasma concentration ( C _max) and area under the concentration–time curve from time zero to time t (AUC_ t ) of Doxylamine hydrogen succinate 12.5 mg and 25 mg tablets increased linearly and dose-dependently [12.5 mg: mean C _max 61.94 ng/mL, coefficient of variation (CV) 23.2 %; mean AUC_ t 817.33 ng·h/mL, CV 27.4 %; and 25 mg: mean C _max 124.91 ng/mL, CV 18.7 %; mean AUC_ t 1630.85 ng·h/mL, CV 22.8 %]. Mean AUC_ t normalized was 815.43 ng·h/mL, CV 22.8 % for 25 mg. The dose-normalized geometric mean ratio (%, 12.5 mg/25 mg) of AUC_ t was 98.92 (90 % CI: 92.46, 105.83). The most common adverse event was somnolence. Conclusions Exposure to Doxylamine was proportional over the therapeutic dose range of 12.5–25 mg in healthy volunteers. Based on the results, a predictable and linear increase in systemic exposure can be expected. Doxylamine hydrogen succinate was safe and well tolerated.
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Pharmacokinetic Dose Proportionality Between Two Strengths (12.5 mg and 25 mg) of Doxylamine Hydrogen Succinate Film- Coated Tablets in Fasting State: A Single-Dose, Randomized, Two-Period Crossover Study in Healthy Volunteers
Drugs in R&D, 2013Co-Authors: Sebastián Videla, Mounia Lahjou, Pascal Guibord, Gregorio Encina, Eric Sicard, Jesús Cebrecos, Anna Cabot, Mercedes Encabo, Artur SansAbstract:Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of Doxylamine are available, although this drug has been marketed in European countries for more than 50 years.
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Food effects on the pharmacokinetics of Doxylamine hydrogen succinate 25 mg film-coated tablets: a single-dose, randomized, two-period crossover study in healthy volunteers.
Drugs in R&D, 2012Co-Authors: Sebastián Videla, Mounia Lahjou, Pascal Guibord, Carles Tolrà, Gregorio Encina, Eric Sicard, Artur SansAbstract:Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the pharmacokinetic profile of Doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, no data on the effect of food on the pharmacokinetic parameters of Doxylamine are available.
Ching Hsia Hung - One of the best experts on this subject based on the ideXlab platform.
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spinal sensory and motor blockade by intrathecal Doxylamine and triprolidine in rats
Journal of Pharmacy and Pharmacology, 2018Co-Authors: Jann Inn Tzeng, Chong Chi Chiu, Jhijoung Wang, Ching Hsia Hung, Yu Wen ChenAbstract:OBJECTIVES The aim of this experiment was mainly to examine the effects of intrathecally injected Doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions. METHODS After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with Doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with Doxylamine or triprolidine were conducted. KEY FINDINGS Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine > mepivacaine > Doxylamine (P < 0.05) at provoking spinal motor, proprioceptive and nociceptive blockades. On the equianaesthetic doses (ED25 , ED50 and ED75 ), the duration of spinal anaesthesia with Doxylamine was longer (P < 0.01) than that with mepivacaine or triprolidine. Moreover, Doxylamine or triprolidine displayed greater potency (ED50 ) (P < 0.05) and duration (P < 0.05) of sensory block over motor block. CONCLUSIONS Doxylamine or triprolidine produces a dose-dependent effect of spinal motor and sensory block. Triprolidine with a better nociception-selective action over motor block has a better potency than mepivacaine or Doxylamine. Doxylamine and triprolidine produce longer durations than mepivacaine.
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Spinal sensory and motor blockade by intrathecal Doxylamine and triprolidine in rats.
The Journal of pharmacy and pharmacology, 2018Co-Authors: Jann Inn Tzeng, Chong Chi Chiu, Jhijoung Wang, Ching Hsia Hung, Yu Wen ChenAbstract:OBJECTIVES The aim of this experiment was mainly to examine the effects of intrathecally injected Doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions. METHODS After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with Doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with Doxylamine or triprolidine were conducted. KEY FINDINGS Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine > mepivacaine > Doxylamine (P
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Subcutaneous infiltration of Doxylamine on cutaneous analgesia in rats
Pharmacological Reports, 2018Co-Authors: Ching Hsia Hung, Chong Chi Chiu, Jhijoung Wang, Ja-ping Shieh, Yu Wen ChenAbstract:Background We aimed to evaluate the effect of Doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. Methods After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of Doxylamine, we assessed Doxylamine’s cutaneous analgesic effect in rats. The dose-related effect and duration of Doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. Results We demonstrated that Doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED_50)), the relative potency was bupivacaine (0.41 (0.36–0.48) mmol)> Doxylamine (7.39 (6.91–7.91) mmol) ( p < 0.01). On an equipotent basis (ED_25, ED_50 and ED_75), subcutaneous Doxylamine resulted in greater duration of action ( p < 0.01) than bupivacaine at producing cutaneous analgesia. Conclusions The result of this experiment indicated that Doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.
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Subcutaneous infiltration of Doxylamine on cutaneous analgesia in rats.
Pharmacological reports : PR, 2017Co-Authors: Ching Hsia Hung, Chong Chi Chiu, Jhijoung Wang, Ja-ping Shieh, Yu Wen ChenAbstract:Abstract Background We aimed to evaluate the effect of Doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. Methods After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of Doxylamine, we assessed Doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of Doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. Results We demonstrated that Doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36–0.48) mmol)> Doxylamine (7.39 (6.91–7.91) mmol) (p Conclusions The result of this experiment indicated that Doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.
Ilan Matok - One of the best experts on this subject based on the ideXlab platform.
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Maternal safety of the delayed-release Doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial
BMC pregnancy and childbirth, 2015Co-Authors: Gideon Koren, Shannon Clark, Steve Caritis, Jason Umans, Menachem Miodovnik, Gary D V Hankins, Donald R. Mattison, Ilan MatokAbstract:Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of Doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of Doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo. We randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2–4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing. Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement. Doxylamine succinate–pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy. Clinical Trial Registration No: NCT00614445 .
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comparing the pharmacokinetics of Doxylamine pyridoxine delayed release combination in nonpregnant women of reproductive age and women in the first trimester of pregnancy
The Journal of Clinical Pharmacology, 2013Co-Authors: Shannon Clark, Steve Caritis, Jason Umans, Ilan Matok, Menachem Miodovnik, Gideon Koren, Gary D V HankinsAbstract:Although Diclectin (Doxylamine/pyridoxine delayed-released combination) is widely used in Canada, its pharmacokinetics (PK) during pregnancy has never been described. The objective of this study was to compare the PK of Doxylamine/pyridoxine delayed-released combination in pregnant versus nonpregnant women. The apparent clearances (CL) of Doxylamine and pyridoxal 5'-phosphate (PLP; the active metabolite of vitamin B(6) ) during the first-trimester pregnancy in women who participated in a Diclectin randomized trial were compared with those of healthy, adult, nonpregnant women who participated in a voluntary PK trial. Eighteen nonpregnant women were compared with 50 pregnant women who were treated with Diclectin. There was no difference in the apparent CL of Doxylamine in women in their first trimester of pregnancy when compared with nonpregnant women on day 4 (median = 196.7 vs 249.5 mL/h/kg, respectively, P = .065), day 8 (median = 248.4 vs 249.5 mL/h/kg, respectively, P = .82), and day 15 (median = 200.9 vs 249.5 mL/h/kg, respectively, P = .55). No difference was found in the apparent CL of PLP on day 15 (median = 342.3 vs 314.7 mL/h/kg, respectively, P = .92). There was no pregnancy-induced effect in the apparent CL of either Doxylamine or PLP in women during the first trimester of pregnancy despite the existence of morning sickness.
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Comparing the Pharmacokinetics of Doxylamine/Pyridoxine Delayed-Release Combination in Nonpregnant Women of Reproductive Age and Women in the First Trimester of Pregnancy
The Journal of Clinical Pharmacology, 2013Co-Authors: Ilan Matok, Shannon Clark, Gary Hankins, Steve Caritis, Jason Umans, Menachem Miodovnik, Gideon KorenAbstract:Although Diclectin (Doxylamine/pyridoxine delayed-released combination) is widely used in Canada, its pharmacokinetics (PK) during pregnancy has never been described. The objective of this study was to compare the PK of Doxylamine/pyridoxine delayed-released combination in pregnant versus nonpregnant women. The apparent clearances (CL) of Doxylamine and pyridoxal 5'-phosphate (PLP; the active metabolite of vitamin B(6) ) during the first-trimester pregnancy in women who participated in a Diclectin randomized trial were compared with those of healthy, adult, nonpregnant women who participated in a voluntary PK trial. Eighteen nonpregnant women were compared with 50 pregnant women who were treated with Diclectin. There was no difference in the apparent CL of Doxylamine in women in their first trimester of pregnancy when compared with nonpregnant women on day 4 (median = 196.7 vs 249.5 mL/h/kg, respectively, P = .065), day 8 (median = 248.4 vs 249.5 mL/h/kg, respectively, P = .82), and day 15 (median = 200.9 vs 249.5 mL/h/kg, respectively, P = .55). No difference was found in the apparent CL of PLP on day 15 (median = 342.3 vs 314.7 mL/h/kg, respectively, P = .92). There was no pregnancy-induced effect in the apparent CL of either Doxylamine or PLP in women during the first trimester of pregnancy despite the existence of morning sickness.