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Doxylamine; Pyridoxine
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20 mg doxylamine; 20 mg pyridoxine PO once daily PO at bedtime, initially. May increase the dose to 10 mg doxylamine; 10 mg pyridoxine PO once daily in the morning and 20 mg doxylamine; 20 mg pyridoxine PO once daily at bedtime starting on day 3 if symptoms persist. May further increase the dose to 10 mg doxylamine; 10 mg pyridoxine PO twice daily in the morning and mid-afternoon and 20 mg doxylamine; 20 mg pyridoxine PO once daily at bedtime if symptoms persist. Max: 40 mg/day doxylamine; 40 mg/day pyridoxine.[54146] [66066]
20 mg doxylamine; 20 mg pyridoxine PO once daily at bedtime, initially. May increase the dose to 20 mg doxylamine; 20 mg pyridoxine PO twice daily on day 2 if symptoms persist. Max: 40 mg/day doxylamine; 40 mg/day pyridoxine.[63316] [66066]
40 mg/day doxylamine; 40 mg/day pyridoxine PO.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
† Off-label indication
Doxylamine; pyridoxine is an oral combination of an antihistamine and vitamin B6 analog indicated for the treatment of nausea and vomiting of pregnancy in individuals who do not respond to conservative management. Doxylamine is a sedating antihistamine (H-1 receptor antagonist) of the ethanolamine class; pyridoxine is also known as vitamin B6. Epidemiological studies have shown no increased risk of teratogenicity with combined use of doxylamine and pyridoxine. Clinical evaluation of doxylamine; pyridoxine was limited to pregnancy within 14 weeks; it is important to reassess the continued need for therapy as pregnancy progresses. Doxylamine may cause marked drowsiness. Therefore, individuals receiving doxylamine; pyridoxine should avoid engaging in activities requiring mental alertness, such as driving or operating heavy machinery, until cleared to do so by their health care provider.[54146][63316] Guidelines suggest doxylamine; pyridoxine as a first-line pharmacologic agent for nausea and vomiting due to pregnancy.[66066] Doxylamine; pyridoxine was FDA-approved in 1976.[54146][63316]
For storage information, see the specific product information within the How Supplied section.
Drowsiness was reported in 14.3% of subjects receiving doxylamine; pyridoxine during clinical studies. Other nervous system adverse events reported with doxylamine; pyridoxine in postmarketing experience include dizziness, headache, migraine, paresthesias, and psychomotor hyperactivity (restlessness). Psychiatric adverse events reported with doxylamine; pyridoxine in postmarketing experience include anxiety, disorientation, insomnia, and nightmares.[54146] [63316]
Special senses adverse reactions reported with doxylamine; pyridoxine in postmarketing experience include blurred vision, visual disturbances, and vertigo.[54146] [63316]
Gastrointestinal adverse events reported with doxylamine; pyridoxine in postmarketing experience include abdominal distension, abdominal pain, constipation, and diarrhea.[54146] [63316]
Cardiac adverse events reported with doxylamine; pyridoxine in postmarketing experience include dyspnea, palpitations, and sinus tachycardia.[54146] [63316]
Renal and urinary adverse events reported with doxylamine; pyridoxine in postmarketing experience include dysuria and urinary retention.[54146] [63316]
Skin and subcutaneous tissue disorders reported with doxylamine; pyridoxine in postmarketing experience include hyperhidrosis, pruritus, rash, and maculopapular rash.[54146] [63316]
General adverse reactions reported with doxylamine; pyridoxine in postmarketing experience include chest discomfort, fatigue, hypersensitivity, irritability, and malaise.[54146] [63316]
Advise individuals receiving doxylamine; pyridoxine to avoid driving or operating machinery until cleared to do so. Doxylamine; pyridoxine may cause somnolence due to the anticholinergic properties of doxylamine, a sedating antihistamine.[54146] [63316]
Use doxylamine; pyridoxine with caution in individuals with increased intraocular pressure, closed-angle glaucoma, stenosing peptic ulcer disease, GI obstruction (pyloroduodenal obstruction), and bladder obstruction. Doxylamine; pyridoxine has anticholinergic properties and may worsen symptoms of these medical conditions.[54146] [63316]
Doxylamine; pyridoxine is contraindicated in individuals who are receiving concomitant monoamine oxidase inhibitors (MAOI therapy). MAOIs may intensify and prolong the adverse anticholinergic and central nervous system effects of doxylamine.[54146] [63316]
Doxylamine; pyridoxine use is associated with laboratory test interference. False positive urine screening tests for methadone or other opioids and phencyclidine phosphate (PCP) can occur with doxylamine; pyridoxine use. Confirmatory tests, such as gas chromatography mass spectrometry (GC-MS), should be used to confirm the identity of the substance in the event of a positive immunoassay result.[63316]
Doxylamine; pyridoxine is intended for use during pregnancy.[54146] [63316] [66066] No increased risk for congenital malformations has been reported in epidemiologic studies in pregnant individuals. Doxylamine; pyridoxine has been evaluated through epidemiological studies (cohort, case control and meta-analyses) designed to detect possible teratogenicity. A meta-analysis of 16 cohort and 11 case-control studies reported no increased risk for malformations from first trimester exposures to doxylamine and pyridoxine, with or without dicyclomine. A second meta-analysis of 12 cohort and 5 case-control studies reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine and pyridoxine with or without dicyclomine.[54146] [63316]
Breast-feeding is not recommended during doxylamine; pyridoxine therapy. The molecular weight of doxylamine succinate is low enough that passage into breast milk can be expected. Excitement, irritability, and sedation have been reported in breast-fed infants presumably exposed to doxylamine through breast milk. Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of doxylamine; pyridoxine resulting in worsening of their apnea or respiratory conditions. Pyridoxine is excreted into breast milk. There have been no reports of adverse events in infants presumably exposed to pyridoxine through breast milk.[54146] [63316]
The mechanism of action of doxylamine; pyridoxine for the treatment of pregnancy-induced nausea/vomiting is unknown.[54146]
Doxylamine: Doxylamine does not prevent the release of histamine, but it competes with free histamine for binding at the H1-receptor sites. Like other antihistamines, doxylamine competitively antagonizes the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. Unlike second generation antihistamines such as loratadine and cetirizine which selectively block peripheral H1-receptors, first generation antihistamines such as doxylamine bind non-selectively to H1-receptors centrally and peripherally. Thus, sedative effects are more likely to occur with first generation antihistamines, especially the ethanolamine group. Doxylamine belongs to the ethanolamine group. Following prolonged use, tolerance can occur, but this may be beneficial, dependent on the indication for drug use, because of reduced sedative effects.
H1-antagonists are structurally similar to anticholinergic agents and therefore possess anticholinergic properties of varying degrees. Ethanolamine derivatives such as doxylamine have greater anticholinergic activity than do other antihistamines and commonly produce side effects such as dry mouth, blurred vision, constipation and urinary retention. These anticholinergic actions appear to be due to a central antimuscarinic effect which also may be responsible for the antiemetic effects seen with this class, although the exact mechanism is unknown.
Pyridoxine:Vitamin B6 is composed of pyridoxine, pyridoxal, and pyridoxamine, and foods usually contain all three forms. Pyridoxine is converted in erythrocytes to the active moiety, pyridoxal phosphate (requiring riboflavin for the conversion), while pyridoxamine is converted into pyridoxamine phosphate. These active forms act as coenzymes for no fewer than 60 metabolic processes including the metabolism of fat, protein, and carbohydrate. Their role in protein metabolism includes decarboxylation of amino acids, conversion of tryptophan to niacin or serotonin, deamination, and transamination of amino acids. In carbohydrate metabolism, it is necessary for the conversion of glycogen to glucose-1-phosphate. Pyridoxine is essential for synthesis of gamma aminobutyric acid (GABA) in the CNS and synthesis of heme.
Revision Date: 12/07/2024, 01:50:00 AMDoxylamine; pyridoxine is administered orally. Pyridoxine is highly protein bound, primarily to albumin. Its main active metabolite, pyridoxal 5'-phosphate (PLP) accounts for at least 60% of circulating vitamin B6 concentrations. Doxylamine is biotransformed in the liver by N-dealkylation to the principal metabolites N-desmethyldoxylamine and N, N-didesmethyldoxylamine. Pyridoxine is a prodrug primarily metabolized in the liver. The principal metabolites of doxylamine are excreted by the kidney. The terminal elimination half-lives of doxylamine and pyridoxine are 11.9 to 12.5 hours and 0.4 to 0.5 hours, respectively.[54146][63316]
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: none
Doxylamine and pyridoxine are absorbed in the gastrointestinal tract, mainly in the jejunum. The times to reach peak concentrations (Tmax) of doxylamine and pyridoxine in healthy, non-pregnant individuals were within 7.5 and 5.5 hours, respectively. Multiple-dose administration results in increased concentrations (Cmax) and exposure (AUC) of doxylamine; Tmax is not affected. The mean accumulation index for doxylamine is more than 1 suggesting it accumulates after multiple doses. Although no accumulation was observed for pyridoxine, the mean accumulation index for each metabolite is more than 1 after multiple-dose administration of the combination product; the Tmax for pyridoxine is not affected by multiple doses.[54146] A single-dose of doxylamine 20 mg; pyridoxine 20 mg extended-release tablet taken under fasting conditions in healthy, premenopausal individuals was determined to be bioequivalent to 2 tablets of doxylamine 10 mg; pyridoxine 10 mg based on the AUC and Cmax of doxylamine and baseline corrected pyridoxal 5'-phosphate (PLP). Multiple-dose administration of doxylamine 20 mg; pyridoxine 20 mg extended-release tablets given twice daily for 11 days in healthy, premenopausal individuals was determined to be bioequivalent to doxylamine 10 mg; pyridoxine 10 mg given 3 times daily (1 tablet in the morning, 1 tablet in the afternoon, and 2 tablets at bedtime), based on the AUC and Cmax of doxylamine and baseline corrected PLP.[63316] The administration of food delays the absorption of both doxylamine and pyridoxine.[54146][63316]
The effect of hepatic impairment on the pharmacokinetics of doxylamine; pyridoxine has not been studied.[54146][63316]
The effect of renal impairment on the pharmacokinetics of doxylamine; pyridoxine has not been studied.[54146][63316]
The effect of race on the pharmacokinetics of doxylamine; pyridoxine has not been studied.[54146][63316]
Doxylamine; pyridoxine is intended for use during pregnancy.[54146] [63316] [66066] No increased risk for congenital malformations has been reported in epidemiologic studies in pregnant individuals. Doxylamine; pyridoxine has been evaluated through epidemiological studies (cohort, case control and meta-analyses) designed to detect possible teratogenicity. A meta-analysis of 16 cohort and 11 case-control studies reported no increased risk for malformations from first trimester exposures to doxylamine and pyridoxine, with or without dicyclomine. A second meta-analysis of 12 cohort and 5 case-control studies reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine and pyridoxine with or without dicyclomine.[54146] [63316]
Breast-feeding is not recommended during doxylamine; pyridoxine therapy. The molecular weight of doxylamine succinate is low enough that passage into breast milk can be expected. Excitement, irritability, and sedation have been reported in breast-fed infants presumably exposed to doxylamine through breast milk. Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of doxylamine; pyridoxine resulting in worsening of their apnea or respiratory conditions. Pyridoxine is excreted into breast milk. There have been no reports of adverse events in infants presumably exposed to pyridoxine through breast milk.[54146] [63316]
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