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DRUGS & SUPPLEMENTS
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Acetaminophen:
Nighttime Cold and Flu is an analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, the predominant influence on the thermoregulation center in the hypothalamus, enhances heat transfer.
Pain weak and moderate intensity of different genesis (including headache, migraine, toothache, neuralgia, myalgia, algomenorrhea; pain in trauma, burns). Fever in infectious and inflammatory diseases.
Oral or rectally adults and adolescents with a body weight over 60 kg is used in a single dose of 500 mg, the multiplicity of admission - up to 4 times / Maximum duration of treatment - 5-7 days.
Maximum dose: single - 1 g, daily - 4 g.
Single dose for oral administration for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg. Single dose rectal in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.
Multiplicity - 4 at intervals of not less than 4 h. The maximum duration of treatment - 3 days.
Maximum dose: 4 single dose per day.
Digestive system: rarely - dyspepsia; long-term use at high doses - hepatotoxic effects, methemoglobinemia, renal dysfunction and liver, hypochromic anemia. Hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis. Allergic reactions: rarely - skin rash, itching, hives.
Chronic active alcoholism, increased sensitivity to Nighttime Cold and Flu, marked disturbances of liver function and / or kidney disease, anemia, pregnancy (I term).
Nighttime Cold and Flu (Acetaminophen) crosses the placental barrier. So far, no observed adverse effects of Nighttime Cold and Flu (Acetaminophen) on the fetus in humans.
Nighttime Cold and Flu (Acetaminophen) is excreted in breast milk: the content in milk was 0.04-0.23% of the dose adopted mother.
If necessary, use of Nighttime Cold and Flu (Acetaminophen) during pregnancy and lactation (breastfeeding) should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus or child.
In experimental studies found no embryotoxic, teratogenic and mutagenic action of Nighttime Cold and Flu (Acetaminophen).
Nighttime Cold and Flu is used with caution in patients with disorders of the liver and kidneys, with benign hyperbilirubinemia, as well as in elderly patients.
With prolonged use of Nighttime Cold and Flu (Acetaminophen) is necessary to monitor patterns of peripheral blood and functional state of the liver.
Used for treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, a derivative of xanthine) and mepyramine (Histamine H1-receptors blocker).
With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic action of Nighttime Cold and Flu (Acetaminophen).
With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.
With the simultaneous use of anticholinergics may decrease absorption of Nighttime Cold and Flu (Acetaminophen).
With the simultaneous use of oral contraceptives accelerated excretion of Nighttime Cold and Flu (Acetaminophen) from the body and may reduce its analgesic action.
With the simultaneous use with urological means reduced their effectiveness.
With the simultaneous use of activated charcoal reduced bioavailability of Nighttime Cold and Flu (Acetaminophen).
When Nighttime Cold and Flu (Acetaminophen) applied simultaneously with diazepam may decrease excretion of diazepam.
There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with Nighttime Cold and Flu (Acetaminophen). A case of severe toxic liver injury.
Described cases of toxic effects of Nighttime Cold and Flu (Acetaminophen), while the use of isoniazid.
When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of Nighttime Cold and Flu (Acetaminophen), which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of Nighttime Cold and Flu (Acetaminophen) and phenobarbital.
In applying cholestyramine a period of less than 1 h after administration of Nighttime Cold and Flu (Acetaminophen) may decrease of its absorption.
At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.
With the simultaneous use of metoclopramide may increase absorption of Nighttime Cold and Flu (Acetaminophen) and its increased concentration in blood plasma.
When applied simultaneously with probenecid may decrease clearance of Nighttime Cold and Flu (Acetaminophen), with rifampicin, sulfinpyrazone - may increase clearance of Nighttime Cold and Flu (Acetaminophen) due to increasing its metabolism in the liver.
At simultaneous application of Nighttime Cold and Flu (Acetaminophen) with ethinylestradiol increases absorption of Nighttime Cold and Flu (Acetaminophen) from the gut.
Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).
At a reception in toxic doses (10-15 g in adults) may develop liver necrosis.
Symptoms of overdose may include: nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, flu-like symptoms
Dextromethorphan Hydrobromide:
Nighttime Cold and Flu is an antitussive medication. Inhibiting the excitability of the cough center this medicine suppresses the cough of any origin. Nighttime Cold and Flu (Dextromethorphan Hydrobromide) has not addiction effects and it has no analgesic and hypnotic action. Nighttime Cold and Flu (Dextromethorphan Hydrobromide) starts to act after 10-30 minutes after oral administration, the duration of therapeutic action: 5-6 hours for adults and 6-9 hours for children. Nighttime Cold and Flu (Dextromethorphan Hydrobromide) is an optical isomer of levomethorphan which is similar to morphine. Due to optical isomerism this drug has no opioid effects. Nighttime Cold and Flu (Dextromethorphan Hydrobromide) used mainly for replacement of codeine as a cough suppressant. In addition to the cough suppressant this medication is used in medicine for diagnostic purposes and may be useful in various cases - from seizures to heroin addiction treatment, some chronic neurodegenerative diseases. These include amyotrophic lateral sclerosis (ALS) (Charcot's disease), disease of "mad cow and other prion diseases. Nighttime Cold and Flu (Dextromethorphan Hydrobromide) has also been used for the treatment of mental retardation, Parkinson's disease, in the treatment of lung and other cancers and to prevent tissue rejection in transplantation because of the (poorly known) effects of sigma ligands on tumor cells and immune system.
After oral administration Nighttime Cold and Flu (Dextromethorphan Hydrobromide) is completely absorbed from the gastrointestinal tract. Cmax of Nighttime Cold and Flu (Dextromethorphan Hydrobromide) in plasma is reached after 2 h. This medication biotransformes in the liver. Up to 45% of this drug is excreted by kidneys and there was considerable individual variation in rates of excretion of individual metabolites.
Dry cough of different etiology.
For adults and children over 12 years Nighttime Cold and Flu prescribed on 15 mg 4 times / day, children aged 6 years - 7.5 mg 4 times / day.
Drowsiness, nausea, dizziness.
Bronchial asthma, bronchitis, simultaneous reception of mucolytic.
During pregnancy and lactation (breastfeeding) Nighttime Cold and Flu (Dextromethorphan Hydrobromide) prescribed with caution, only in cases where the expected therapeutic effect for the mother outweighs the potential risk to the fetus or child.
With carefully administered Nighttime Cold and Flu (Dextromethorphan Hydrobromide) with impaired liver function.
MAO inhibitors (including furazolidone, procarbazine, selegiline) when administered simultaneous with Nighttime Cold and Flu (Dextromethorphan Hydrobromide) may cause adrenergic crisis, collapse, coma, dizziness, agitation, increased blood pressure, hyperpyrexia, intracranial hemorrhage, lethargy, nausea, cramps, tremor. In combination with tricyclic antidepressants (amitriptyline, etc.) Nighttime Cold and Flu (Dextromethorphan Hydrobromide) may appeal serotonin syndrome and possible subsequent death. Amiodarone, fluoxetine, quinidine, inhibiting system cytochrome P450, may increase the drug concentration in the blood. Tobacco smoke can lead to increased secretion of glands in the background of inhibition of cough reflex. Some inhibitors of CYP450 (such as quinidine) increase and extended effects of this medicine.
Symptoms: excitement, dizziness, respiratory depression, impaired consciousness, decreased blood pressure, tachycardia, muscle hypertonicity, ataxia.
Treatment: mechanical ventilation, symptomatic agents.
Doxylamine Succinate:
Nighttime Cold and Flu (Doxylamine Succinate) is indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management.
Limitations of Use
Nighttime Cold and Flu (Doxylamine Succinate) has not been studied in women with hyperemesis gravidarum.
Nighttime Cold and Flu (Doxylamine Succinate) is a fixed dose combination drug product of Nighttime Cold and Flu (Doxylamine Succinate) succinate, an antihistamine, and pyridoxine hydrochloride, a Vitamin B6 analog, indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management. (1)
Take two tablets daily at bedtime. If symptoms are not adequately controlled, the dose can be increased to a maximum recommended dose of four tablets daily as described in the full prescribing information. (2)
Initially, take two Nighttime Cold and Flu (Doxylamine Succinate) delayed-release tablets orally at bedtime (Day 1). If this dose adequately controls symptoms the next day, continue taking two tablets daily at bedtime. However, if symptoms persist into the afternoon of Day 2, take the usual dose of two tablets at bedtime that night then take three tablets starting on Day 3 (one tablet in the morning and two tablets at bedtime). If these three tablets adequately control symptoms on Day 4, continue taking three tablets daily. Otherwise take four tablets starting on Day 4 (one tablet in the morning, one tablet mid-afternoon and two tablets at bedtime).
The maximum recommended dose is four tablets (one in the morning, one in the mid-afternoon and two at bedtime) daily.
Take on an empty stomach with a glass of water . Swallow tablets whole. Do not crush, chew, or split Nighttime Cold and Flu (Doxylamine Succinate) tablets.
Take as a daily prescription and not on an as needed basis. Reassess the woman for continued need for Nighttime Cold and Flu (Doxylamine Succinate) as her pregnancy progresses.
Nighttime Cold and Flu (Doxylamine Succinate) delayed-release tablets are white, round, film coated tablets containing 10 mg Nighttime Cold and Flu (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride. The tablets are imprinted with the pink image of a pregnant woman on one side.
Delayed-release tablets containing 10 mg Nighttime Cold and Flu (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride. (3)
Nighttime Cold and Flu (Doxylamine Succinate) is contraindicated in women with any of the following conditions:
Nighttime Cold and Flu (Doxylamine Succinate) may cause somnolence due to the anticholinergic properties of Nighttime Cold and Flu (Doxylamine Succinate) succinate, an antihistamine. Women should avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using Nighttime Cold and Flu (Doxylamine Succinate) until cleared to do so by their healthcare provider.
Nighttime Cold and Flu (Doxylamine Succinate) use is not recommended if a woman is concurrently using central nervous system (CNS) depressants including alcohol. The combination may result in severe drowsiness leading to falls or accidents .
Nighttime Cold and Flu (Doxylamine Succinate) has anticholinergic properties and, therefore, should be used with caution in women with: asthma, increased intraocular pressure, narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction and urinary bladder-neck obstruction.
The most common adverse reaction with Nighttime Cold and Flu (Doxylamine Succinate) (≥5 percent and exceeding the rate in placebo) is somnolence. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Duchesnay Inc. at 1-855-722-7734 or medicalinfoNighttime Cold and Flu (Doxylamine Succinate)duchesnayusa.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety and efficacy of Nighttime Cold and Flu (Doxylamine Succinate) were compared to placebo in a double-blind, randomized, multi-center trial in 261 women with nausea and vomiting of pregnancy. The mean gestational age at enrollment was 9.3 weeks, range 7 to 14 weeks gestation . Adverse reactions for Nighttime Cold and Flu (Doxylamine Succinate) that occurred at an incidence ≥5 percent and exceeded the incidence for placebo are summarized in Table 1.
Table 1: Number (Percent) of Subjects with ≥ 5 Percent Adverse Reactions in a 15‑Day Placebo-Controlled Study of Nighttime Cold and Flu (Doxylamine Succinate) (Only Those Adverse Reactions Occurring at an Incidence ≥ 5 Percent and at a Higher Incidence with Nighttime Cold and Flu (Doxylamine Succinate) than Placebo are Shown)
Nighttime Cold and Flu (Doxylamine Succinate) (N = 133) | Placebo (n = 128) | |
Somnolence | 19 (14.3%) | 15 (11.7%) |
The following adverse events, listed alphabetically, have been identified during post-approval use of the combination of 10 mg Nighttime Cold and Flu (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac disorders: dyspnea, palpitation, tachycardia
Ear and labyrinth disorders: vertigo
Eye disorders: vision blurred, visual disturbances
Gastrointestinal disorders: abdominal distension, abdominal pain, constipation, diarrhea
General disorders and administration site conditions: chest discomfort, fatigue, irritability, malaise
Immune system disorders: hypersensitivity
Nervous system disorders: dizziness, headache, migraines, paresthesia, psychomotor hyperactivity
Psychiatric disorders: anxiety, disorientation, insomnia, nightmares
Renal and urinary disorders: dysuria, urinary retention
Skin and subcutaneous tissue disorders: hyperhidrosis, pruritus, rash, rash maculo-papular
Use of Nighttime Cold and Flu (Doxylamine Succinate) is contraindicated in women who are taking monoamine oxidase inhibitors (MAOIs), which prolong and intensify the anticholinergic (drying) effects of antihistamines. Concurrent use of alcohol and other CNS depressants (such as hypnotic sedatives and tranquilizers) with Nighttime Cold and Flu (Doxylamine Succinate) is not recommended.
A food-effect study demonstrated that the delay in the onset of action of Nighttime Cold and Flu (Doxylamine Succinate) may be further delayed, and a reduction in absorption may occur when tablets are taken with food . Therefore, Nighttime Cold and Flu (Doxylamine Succinate) should be taken on an empty stomach with a glass of water [ see Dosage and Administration (2)].
Pregnancy Category A. Nighttime Cold and Flu is intended for use in pregnant women. (8.1)
Pregnancy Category A
Nighttime Cold and Flu (Doxylamine Succinate) is intended for use in pregnant women.
The combination of Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride has been the subject of many epidemiological studies (cohort, case control and meta-analyses) designed to detect possible teratogenicity. A meta-analysis of 16 cohort and 11 case-control studies published between 1963 and 1991 reported no increased risk for malformations from first trimester exposures to Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride, with or without dicyclomine hydrochloride. A second meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride.
Animal Data
The effects of Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride on embryofetal development have been studied in rats and monkeys.
Once daily treatment of pregnant rats with Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride during organogenesis (gestational day (GD) 6-15) resulted in increased fetal resorptions, decreased fetal body weight and increased skeletal variations with reduced ossification at doses 60 to 100 times the highest clinical dose based on body surface area.
Pregnant cynomolgus monkeys were treated once daily with Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride during organogenesis (GD 22-50). At birth, there were no observed malformations, and no evidence of embryo, fetal or maternal toxicity at doses up to 3.2 times the highest proposed clinical dose based on body surface area. In a similarly designed study in pregnant cynomolgus and rhesus monkeys and baboons, ventricular septal defects (VSDs) were observed in the preterm (GD 100) fetuses. Doses used in this study were 0.5-20 times higher than the clinical dose based on body surface area, with no relationship between dose and incidence of VSD. There were no VSDs in infant monkeys at term. No VSDs were observed at GD 100 in cynomolgus monkeys administered the combination of Nighttime Cold and Flu (Doxylamine Succinate) succinate and pyridoxine hydrochloride for 4-day periods between 22 and 41 days of gestation.
Women should not breastfeed while using Nighttime Cold and Flu.
The molecular weight of Nighttime Cold and Flu (Doxylamine Succinate) succinate is low enough that passage into breast milk can be expected. Excitement, irritability and sedation have been reported in nursing infants presumably exposed to Nighttime Cold and Flu (Doxylamine Succinate) succinate through breast milk. Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of Nighttime Cold and Flu (Doxylamine Succinate) resulting in worsening of their apnea or respiratory conditions.
Pyridoxine hydrochloride is excreted into breast milk. There have been no reports of adverse events in infants presumably exposed to pyridoxine hydrochloride through breast milk.
The safety and effectiveness of Nighttime Cold and Flu (Doxylamine Succinate) in children under 18 years of age have not been established.
Fatalities have been reported from Nighttime Cold and Flu (Doxylamine Succinate) overdose in children. The overdose cases have been characterized by coma, grand mal seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3 year old child died 18 hours after ingesting 1,000 mg Nighttime Cold and Flu (Doxylamine Succinate) succinate. However, there is no correlation between the amount of Nighttime Cold and Flu (Doxylamine Succinate) ingested, the Nighttime Cold and Flu (Doxylamine Succinate) plasma level and clinical symptomatology.
Nighttime Cold and Flu is a delayed-release formulation, therefore, signs and symptoms of intoxication may not be apparent immediately.
Signs and symptoms of overdose may include restlessness, dryness of mouth, dilated pupils, sleepiness, vertigo, mental confusion and tachycardia.
At toxic doses, Nighttime Cold and Flu (Doxylamine Succinate) exhibits anticholinergic effects, including seizures, rhabdomyolysis, acute renal failure and death.
If treatment is needed, it consists of gastric lavage or activated charcoal, whole bowel irrigation and symptomatic treatment. For additional information about overdose treatment, call a poison control center (1‑800-222-1222).
Nighttime Cold and Flu (Doxylamine Succinate) (doxylamine succinate and pyridoxine hydrochloride) delayed-release tablets are round, white, film-coated, delayed-release tablets containing 10 mg of Nighttime Cold and Flu (Doxylamine Succinate) succinate and 10 mg of pyridoxine hydrochloride. Tablets are imprinted on one side with the pink image of a pregnant woman.
Inactive ingredients are as follows: ammonium hydroxide, n-butanol, carnauba wax powder, colloidal silicon dioxide, croscarmellose sodium, D&C Red#27, denatured alcohol, FD&C Blue#2, hypromellose, isopropyl alcohol, magnesium stearate, magnesium trisilicate, methacrylic acid copolymer, microcrystalline cellulose 102, PEG 8000, polysorbate 80, propylene glycol, shellac glaze, simethicone, sodium bicarbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate.
Nighttime Cold and Flu (Doxylamine Succinate) Succinate
Nighttime Cold and Flu (Doxylamine Succinate) succinate is classified as an antihistamine. The chemical name for Nighttime Cold and Flu (Doxylamine Succinate) succinate is ethanamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]-, butanedioate (1:1). The empirical formula is C17H22N2O - C4H6O4 and the molecular mass is 388.46. The structural formula is:
Nighttime Cold and Flu (Doxylamine Succinate) succinate is a white to creamy white powder that is very soluble in water and alcohol, freely soluble in chloroform and very slightly soluble in ether and benzene.
Pyridoxine Hydrochloride
Pyridoxine hydrochloride is a vitamin B6 analog. The chemical name for pyridoxine hydrochloride is 3,4-pyridinedimethanol, 5-hydroxy-6-methyl-, hydrochloride. The empirical formula is C8H11NO3 - HCl and the molecular mass is 205.64. The structural formula is:
Pyridoxine hydrochloride is a white or practically white crystalline powder that is freely soluble in water, slightly soluble in alcohol and insoluble in ether.
The mechanism of action of Nighttime Cold and Flu is unknown.
The pharmacokinetics of Nighttime Cold and Flu (Doxylamine Succinate) has been characterized in healthy non-pregnant adult women. Pharmacokinetic results for Nighttime Cold and Flu (Doxylamine Succinate) and pyridoxine, including its vitamin B6 metabolites, pyridoxal, pyridoxal 5’-phosphate, pyridoxamine and pyridoxamine 5’-phosphate, are summarized in Tables 2 to 5.
Absorption
A single-dose (two tablets) and multiple-dose (four tablets daily), open-label study was conducted to assess the safety and pharmacokinetic profile of Nighttime Cold and Flu (Doxylamine Succinate) administered in healthy non-pregnant adult women. Single-doses (two tablets at bedtime) were administered on Days 1 and 2. Multiple-doses (one tablet in the morning, one tablet in the afternoon and two tablets at bedtime) were administered on Days 3-18.
Blood samples for pharmacokinetic analysis were collected pre-and post-dose on Days 2 and 18 as well as pre-dose prior to bedtime dose only (trough) on Days 9, 10, 11, 16, 17, and 18.
Nighttime Cold and Flu (Doxylamine Succinate) and pyridoxine are absorbed in the gastrointestinal tract, mainly in the jejunum.
The Cmax of Nighttime Cold and Flu (Doxylamine Succinate) and pyridoxine are achieved within 7.5 and 5.5 hours, respectively.
Single Dose | Multiple Dose | |||||
AUC0-inf | Cmax | Tmax | AUC0-inf | Cmax | Tmax | |
(ng-h/mL) | (ng/mL) | (h) | (ng-h/mL) | (ng/mL) | (h) | |
Nighttime Cold and Flu (Doxylamine Succinate) | 1280.9 ± 369.3 | 83.3 ± 20.6 | 7.2 ± 1.9 | 3721.5 ± 1318.5 | 168.6 ± 38.5 | 7.8 ± 1.6 |
Pyridoxine | 43.4 ± 16.5 | 32.6 ± 15.0 | 5.7 ± 1.5 | 64.5 ± 36.4 | 46.1 ± 28.3 | 5.6 ± 1.3 |
Pyridoxal | 211.6 ± 46.1 | 74.3 ± 21.8 | 6.5 ± 1.4 | 1587.2 ± 550.0 | 210.0 ± 54.4 | 6.8 ± 1.2 |
Pyridoxal 5`Phosphate | 1536.4 ± 721.5 | 30.0 ± 10.0 | 11.7 ± 5.3 | 6099.7 ± 1383.7 | 84.9 ± 16.9 | 6.3 ± 6.6 |
Pyridoxamine | 4.1 ± 2.7 | 0.5 ± 0.7 | 5.9 ± 2.1 | 2.6 ± 0.8 | 0.5 ± 0.2 | 6.6 ± 1.4 |
Pyridoxamine 5'-phosphate | 5.2 ± 3.8 | 0.7 ± 0.5 | 14.8 ± 6.6 | 94.5 ± 58.0 | 2.3 ± 1.7 | 12.4 ± 11.2 |
Multiple-dose administration of Nighttime Cold and Flu (Doxylamine Succinate) results in increased concentrations of Nighttime Cold and Flu (Doxylamine Succinate) as well as increases in Nighttime Cold and Flu (Doxylamine Succinate) Cmax and AUC0-last of absorption. The time to reach the maximum concentration is not affected by multiple doses. The mean accumulation index is more than 1.0 suggesting that Nighttime Cold and Flu (Doxylamine Succinate) accumulates following multiple dosing.
Although no accumulation was observed for pyridoxine, the mean accumulation index for each metabolite (pyridoxal, pyridoxal 5’-phosphate, and pyridoxamine 5’-phosphate) is more than 1.0 following multiple-dose administration of Nighttime Cold and Flu (Doxylamine Succinate). The time to reach the maximum concentration is not affected by multiple doses.
AUC0-last (ng-h/mL) | AUC0-inf (ng-h/mL) | Cmax (ng/mL) | Tmax (h) | T1/2el (h) | ||
Nighttime Cold and Flu (Doxylamine Succinate) Mean±SD N=18 | Single | 911.4 ± 205.6 | 1280.9 ± 369.3 | 83.3 ± 20.6 | 7.2 ± 1.9 | 10.1 ± 2.1 |
Multiple | 3661.3 ± 1279.2 | 3721.5 ± 1318.5 | 168.6 ± 38.5 | 7.8 ± 1.6 | 11.9 ± 3.3 | |
Pyridoxine Mean±SD N=18 | Single | 39.3 ± 16.5 | 43.4 ± 16.5 | 32.6 ± 15.0 | 5.7 ± 1.5 | 0.5 ± 0.2 |
Multiple | 59.3 ± 33.9 | 64.5 ± 36.4 | 46.1 ± 28.3 | 5.6 ± 1.3 | 0.5 ± 0.1 |
Food Effect
The administration of food delays the absorption of both Nighttime Cold and Flu (Doxylamine Succinate) and pyridoxine. This delay is associated with a lower peak concentration of Nighttime Cold and Flu (Doxylamine Succinate), but the extent of absorption is not affected.
The effect of food on the peak concentration and the extent of absorption of the pyridoxine component is more complex because the pyridoxal, pyridoxamine, pyridoxal 5’-phosphate and pyridoxamine 5’-phosphate metabolites also contribute to the biological activity. Food significantly reduces the bioavailability of pyridoxine, lowering its Cmax and AUC by approximately 50% compared to fasting conditions. Similarly, food significantly reduces pyridoxal AUC and reduces its Cmax by 50% compared to fasting conditions. In contrast, food slightly increases pyridoxal 5’-phosphate Cmax and extent of absorption. As for pyridoxamine and pyridoxamine 5’-phosphate, the rate and extent of absorption seem to decrease under fed conditions.
AUC0-t (ng-h/mL) | AUC0-inf (ng-h/mL) | Cmax (ng/mL) | Tmax (h) | T1/2el (h) | ||
Nighttime Cold and Flu (Doxylamine Succinate) Mean±SD N=42 | Fasted | 1407.2 ± 336.9 | 1447.9 ± 332.2 | 94.9 ± 18.4 | 5.1 ± 3.4 | 12.6 ± 3.4 |
Fed | 1488.0 ± 463.2 | 1579.0 ± 422.7 | 75.7 ± 16.6 | 14.9 ± 7.4 | 12.5 ± 2.9 | |
Pyridoxine Mean±SD N=42 | Fasted | 33.8 ± 13.7 | 39.5 ± 12.9 | 35.5 ± 21.4 | 2.5 ± 0.9 | 0.4 ± 0.2 |
Fed | 18.3 ± 14.5 | 24.2 ±14.0 | 13.7 ± 10.8 | 9.3 ± 4.0 | 0.5 ± 0.2 |
Distribution
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.
Metabolism
Nighttime Cold and Flu (Doxylamine Succinate) is biotransformed in the liver by N-dealkylation to its principle metabolites N-desmethyl-doxylamine and N, N-didesmethyldoxylamine.
Pyridoxine is a prodrug primarily metabolized in the liver.
Excretion
The principle metabolites of Nighttime Cold and Flu (Doxylamine Succinate), N-desmethyl-doxylamine and N, N-didesmethyldoxylamine, are excreted by the kidney.
The terminal elimination half-life of Nighttime Cold and Flu (Doxylamine Succinate) and pyridoxine are 12.5 hours and 0.5 hours, respectively.
Table 5 – Terminal Elimination Half-Life (T1/2el) for Nighttime Cold and Flu (Doxylamine Succinate) Administered as a Single Dose of Two Tablets under Fasting Conditions in Healthy Non-Pregnant Adult Women
T1/2el (h) | |
Doxylamine | 12.6 ± 3.4 |
Pyridoxine | 0.4 ± 0.2 |
Pyridoxal | 2.1 ± 2.2 |
Pyridoxal 5’-Phosphate | 81.6 ± 42.2 |
Pyridoxamine | 3.1 ± 2.5 |
Pyridoxamine 5’-Phosphate | 66.5 ± 51.3 |
Use in Specific Populations
Race: No pharmacokinetic studies have been conducted related to race.
Hepatic Impairment: No pharmacokinetic studies have been conducted in hepatic impaired patients.
Renal Impairment: No pharmacokinetic studies have been conducted in renal impaired patients.
Carcinogenicity
Two-year carcinogenicity studies in rats and mice have been conducted with Nighttime Cold and Flu (Doxylamine Succinate) succinate. Nighttime Cold and Flu (Doxylamine Succinate) succinate is not likely to have human carcinogenic potential. The carcinogenic potential of pyridoxine hydrochloride has not been evaluated.
A double-blind, randomized, multi-center, placebo-controlled study was conducted to support the safety and efficacy of Nighttime Cold and Flu (Doxylamine Succinate) in the treatment of nausea and vomiting of pregnancy. Adult women 18 years of age or older and 7 to 14 weeks gestation (median 9 weeks of gestation) with nausea and vomiting of pregnancy were randomized to 14 days of Nighttime Cold and Flu (Doxylamine Succinate) or placebo. Two tablets of Nighttime Cold and Flu (Doxylamine Succinate) were administered at bedtime on Day 1. If symptoms of nausea and vomiting persisted into the afternoon hours of Day 2, the woman was directed to take her usual dose of two tablets at bedtime that night and, beginning on Day 3, to take one tablet in the morning and two tablets at bedtime. Based upon assessment of remaining symptoms at her clinic visit on Day 4 (± 1 day), the woman may have been directed to take an additional tablet mid-afternoon. A maximum of four tablets (one in the morning, one in the mid-afternoon and two at bedtime) were taken daily.
Over the treatment period, 19% of DICLEGIS-treated patients remained on 2 tablets daily, 21% received 3 tablets daily, and 60% received 4 tablets daily.
The primary efficacy endpoint was the change from baseline at Day 15 in the Pregnancy Unique-Quantification of Emesis (PUQE) score. The PUQE score incorporates the number of daily vomiting episodes, number of daily heaves, and length of daily nausea in hours, for an overall score of symptoms rated from 3 (no symptoms) to 15 (most severe).
At baseline, the mean PUQE score was 9.0 in the Nighttime Cold and Flu (Doxylamine Succinate) arm and 8.8 in the placebo arm. There was a 0.7 (95% confidence interval 0.2 to 1.2 with p-value 0.006) mean decrease (improvement in nausea and vomiting symptoms) from baseline in PUQE score at Day 15 with Nighttime Cold and Flu (Doxylamine Succinate) compared to placebo.
Table 6 – Change from Baseline in the Primary Endpoint, Pregnancy Unique-Quantification of Emesis (PUQE) Score at Day 15. (Intent-to-Treat Population with Last-Observation Carried Forward)
PUQE Score | Nighttime Cold and Flu (Doxylamine Succinate) Succinate + Pyridoxine Hydrochloride | Placebo | Treatment Difference [95% Confidence Interval] |
Baseline Change from baseline at Day 15 | 9.0 ± 2.1 -4.8 ± 2.7 | 8.8 ± 2.1 -3.9 ± 2.6 | -0.7 [-1.2, -0.2] |
Nighttime Cold and Flu delayed-release tablets are supplied in a high-density polyethylene bottle with a polypropylene child-resistant cap and a silica gel desiccant canister. Each white, round, film-coated, delayed-release tablet contains 10 mg Nighttime Cold and Flu (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride, and is imprinted on one side with the pink image of a pregnant woman. Nighttime Cold and Flu (Doxylamine Succinate) tablets are provided as follows:
NDC 55494-100-10 Bottles of 100.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep bottle tightly closed and protect from moisture. Do not remove desiccant canister from bottle.
See FDA-approved patient labeling
Inform women to avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using Nighttime Cold and Flu (Doxylamine Succinate) until cleared to do so.
Inform women of the importance of not taking Nighttime Cold and Flu (Doxylamine Succinate) with alcohol or sedating medications, including other antihistamines (present in some cough and cold medications), opiates and sleep aids because somnolence could worsen leading to falls or other accidents.
Nighttime Cold and Flu (Doxylamine Succinate)® is a registered trademark of Duchesnay Inc.
U.S. Patent Nos. 6,340,695 & 7,560,122.
Distributed by:
Duchesnay USA, Inc.
Bryn Mawr, PA, 19010
Tel: 1-855-722-7734
Fax: 1-888-588-8508
www.duchesnayusa.com
©2013, Duchesnay Inc. All rights reserved.
Patient Information
Nighttime Cold and Flu (Doxylamine Succinate) (dye-CLEE-gis)
(doxylamine succinate and pyridoxine hydrochloride) delayed-release tablets
What is Nighttime Cold and Flu (Doxylamine Succinate)?
- Nighttime Cold and Flu (Doxylamine Succinate) is a prescription medicine used to treat nausea and vomiting of pregnancy in
women who have not improved with change in diet or other non-medicine treatments.
- It is not known if Nighttime Cold and Flu (Doxylamine Succinate) is safe and effective in children under 18 years of age.
Who should not take Nighttime Cold and Flu (Doxylamine Succinate)?
Do not take Nighttime Cold and Flu (Doxylamine Succinate) if you:
- are allergic to Nighttime Cold and Flu (Doxylamine Succinate) succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any of the ingredients in Nighttime Cold and Flu (Doxylamine Succinate). See the end of this leaflet for a complete list of ingredients in Nighttime Cold and Flu (Doxylamine Succinate).
- take monoamine oxidase inhibitors (MAOIs) (Marplan, Nardil, Emsam, Eldepryl, Zelapar, Parnate)
Before taking Nighttime Cold and Flu (Doxylamine Succinate), tell your healthcare provider about all of your medical conditions, including;
- if you are breastfeeding or plan to breastfeed. Nighttime Cold and Flu (Doxylamine Succinate) can pass into your breast milk and may harm your baby. You should not breastfeed while using Nighttime Cold and Flu (Doxylamine Succinate).
Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, or herbal supplements.
How should I take Nighttime Cold and Flu (Doxylamine Succinate)?
- Talk to your healthcare provider about how much Nighttime Cold and Flu (Doxylamine Succinate) to take and when to take it.
- Take Nighttime Cold and Flu (Doxylamine Succinate) everyday as prescribed by your healthcare provider. Do not stop taking Nighttime Cold and Flu (Doxylamine Succinate) without talking to your healthcare provider first.
- See the following schedule for the usual way you should start taking Nighttime Cold and Flu (Doxylamine Succinate):
- Day 1- Take 2 tablets, by mouth at bedtime.
- Day 2- Take 2 tablets at bedtime. If your nausea and vomiting is better or controlled on Day 2, continue to take 2 tablets every night at bedtime. This will be your usual dose unless your healthcare provider tells you otherwise.
- Day 3- If you still had nausea and vomiting on Day 2, take 3 tablets on Day 3 (1 tablet in the morning and 2 tablets at bedtime).
- Day 4- If your nausea and vomiting was better or controlled on Day 3, continue to take 3 tablets each day (1 tablet in the morning and 2 tablets at bedtime). If you still had nausea and vomiting on Day 3, start taking 4 tablets each day (1 tablet in the morning, 1 tablet in the afternoon, and 2 tablets at bedtime).
- Do not take more than 4 tablets (1 in the morning, 1 in the mid-afternoon, and 2 at bedtime) in 1 day.
- Take Nighttime Cold and Flu (Doxylamine Succinate) on an empty stomach with a glass of water.
- Take Nighttime Cold and Flu (Doxylamine Succinate) tablets whole. Do not crush, chew, or break Nighttime Cold and Flu (Doxylamine Succinate) tablets before swallowing. If you cannot swallow Nighttime Cold and Flu (Doxylamine Succinate) tablets whole, tell your healthcare provider.
- If you take too much Nighttime Cold and Flu (Doxylamine Succinate) (overdose), you may have the following symptoms: restlessness, dry mouth, the pupils of your eyes become larger (dilated), sleepiness, dizziness, confusion, fast heart rate, seizures, muscle pain or weakness, and sudden and severe kidney problems. If you have these symptoms and they are severe, they may lead to death. Stop taking Nighttime Cold and Flu (Doxylamine Succinate), call your healthcare provider or go to the nearest hospital emergency room right away. For more information about overdose treatment, call your poison control center at 1-800-222-1222.
What are the possible side effects of Nighttime Cold and Flu (Doxylamine Succinate)?
Nighttime Cold and Flu (Doxylamine Succinate) may cause serious side effects, including drowsiness.
- Do not drive, operate heavy machinery, or other activities that need your full attention unless your healthcare provider says that you may do so.
- Do not drink alcohol, or take other central nervous system depressants such as cough and cold medicines, certain pain medicines, and medicines that help you sleep while you take Nighttime Cold and Flu (Doxylamine Succinate). Severe drowsiness can happen or become worse causing falls or accidents.
These are not all the possible side effects of Nighttime Cold and Flu (Doxylamine Succinate).
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Nighttime Cold and Flu (Doxylamine Succinate)?
- Store Nighttime Cold and Flu (Doxylamine Succinate) between 68°F to 77°F (20°C to 25°C).
- Keep Nighttime Cold and Flu (Doxylamine Succinate) tablets dry, in a tightly closed container, and out of the light.
- Safely throw away medicine that is out of date or no longer needed.
Keep Nighttime Cold and Flu (Doxylamine Succinate) and all medicines out of the reach of children.
General information about the safe and effective use of Nighttime Cold and Flu (Doxylamine Succinate).
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about Nighttime Cold and Flu (Doxylamine Succinate) that is written for health professionals. Do not use Nighttime Cold and Flu (Doxylamine Succinate) for a condition for which it was not prescribed. Do not give Nighttime Cold and Flu (Doxylamine Succinate) to other people, even if they have the same symptoms that you have. It may harm them.
What are the ingredients in Nighttime Cold and Flu (Doxylamine Succinate)?
Active ingredient: Nighttime Cold and Flu (Doxylamine Succinate) succinate (an antihistamine) and pyridoxine hydrochloride (vitamin B6)
Inactive ingredients: ammonium hydroxide, n-butanol, carnauba wax powder, colloidal silicon dioxide, croscarmellose sodium, D&C Red#27, denatured alcohol, FD&C Blue #2, hypromellose, isopropyl alcohol, magnesium stearate, magnesium trisilicate, methacrylic acid copolymer, microcrystalline cellulose 102, PEG 8000, polysorbate 80, propylene glycol, shellac glaze, simethicone, sodium bicarbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate.
Distributed by: Duchesnay USA, Inc., Bryn Mawr, PA, 19010,
www.duchesnayusa.com or call 1-855-722-7734.
This Patient Information has been approved by the U.S. Food and Drug Administration
Issued: 05/2013
Bottle Label-Outside Front Cover with Imprint Area for Lot & Expiry
Bottle Label – Inside Cover
Pseudoephedrine Hydrochloride:
Active ingredients (in each caplet)...Purpose
Guaifenesin 400 mg...Expectorant
Nighttime Cold and Flu (Pseudoephedrine Hydrochloride) hydrochloride 60 mg...Nasal decongestant
Uses
For temporarily relief of nasal congestion due to a cold, hay fever, or other upper respiratory allergies (allergic rhinitis), and to help loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive.
Uses
Warnings
Do not exceed recommended dosage.
Do not use if you are taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for two weeks after stopping the MAOI. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product.
Do not take this product for persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema, or where cough is accompanied by excessive phlegm (mucus) unless directed by a doctor.
A persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to recur, or is accompanied by fever, rash, or persistent headache, consult a doctor.
Ask a doctor before use if you have
Stop use and ask a doctor if
If pregnant or breast-feeding, ask a health professional before use.
Keep this and all drugs out of reach of children. In case of overdose, get medical help or contact a poison control center immediately.
Directions
Inactive ingredients
croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and starch
Questions?
1-800-324-1880, 7:30am - 4:00pm Central, Mon.-Fri., or visit us at www.bfascher.com
Depending on the reaction of the Nighttime Cold and Flu after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Nighttime Cold and Flu not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Nighttime Cold and Flu addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology