Please wait while the formulary information is being retrieved.
Drug overview for UNISOM (DOXYLAMINE) (doxylamine succinate):
Generic name: doxylamine succinate (dox-IL-a-meen)
Drug class: Antihistamines
Therapeutic class: Central Nervous System Agents
Doxylamine is an ethanolamine-derivative, first generation antihistamine.
Doxylamine succinate shares the actions and uses of other antihistamines.
Generic name: doxylamine succinate (dox-IL-a-meen)
Drug class: Antihistamines
Therapeutic class: Central Nervous System Agents
Doxylamine is an ethanolamine-derivative, first generation antihistamine.
Doxylamine succinate shares the actions and uses of other antihistamines.
DRUG IMAGES
No Image Available
The following indications for UNISOM (DOXYLAMINE) (doxylamine succinate) have been approved by the FDA:
Indications:
Allergic conjunctivitis
Allergic rhinitis
Dermatographic urticaria
Nasal congestion
Pruritus of skin
Rhinorrhea
Sneezing
Urticaria
Professional Synonyms:
Allergy eye itch
Atopic conjunctivitis
Autographism
Cnidosis
Dermatography
Dermographia
Dermographism
Dermography
Ebbecke's reaction
Factitious urticaria
Itching wheals
Itchy eyes due to allergies
Itchy skin eruption
Nasal stuffiness
Nettle rash
Ocular itching due to allergies
Pruritic dermatitis
Skin writing
Uredo
Urticaria factitia
Urticarial rash
Urtication
Weal
Indications:
Allergic conjunctivitis
Allergic rhinitis
Dermatographic urticaria
Nasal congestion
Pruritus of skin
Rhinorrhea
Sneezing
Urticaria
Professional Synonyms:
Allergy eye itch
Atopic conjunctivitis
Autographism
Cnidosis
Dermatography
Dermographia
Dermographism
Dermography
Ebbecke's reaction
Factitious urticaria
Itching wheals
Itchy eyes due to allergies
Itchy skin eruption
Nasal stuffiness
Nettle rash
Ocular itching due to allergies
Pruritic dermatitis
Skin writing
Uredo
Urticaria factitia
Urticarial rash
Urtication
Weal
The following dosing information is available for UNISOM (DOXYLAMINE) (doxylamine succinate):
No enhanced Dosing information available for this drug.
Doxylamine succinate is administered orally. The fixed combination of doxylamine/pyridoxine delayed-release Diclegis(R) and extended-release Bonjesta(R) tablets should be taken on an empty stomach with a glass of water; the tablets should be swallowed whole and should not be crushed, chewed, or split.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for UNISOM (DOXYLAMINE) (doxylamine succinate):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Selected Antihistamines/Selected MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: MAOIs prolong and intensify the effects of antihistamines.(1-6) CLINICAL EFFECTS: Concurrent use of antihistamines and a MAOI may result in severe hypotension.(1-6) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of antihistamines and a MAOI is contraindicated.(1-6) DISCUSSION: MAOIs may prolong and intensify the effects of antihistamines, resulting in severe hypotension.(1-6) A case report describes a patient having cyproheptadine added to their phenelzine therapy in an attempt to relieve the patients anorgasmia. The patient began to suddenly experience visual hallucination after taking the cyproheptadine for two months. Once the medication was terminated, the hallucinations stopped occurring within 48 hours.(7) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(8,9) |
AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR |
There are 6 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Solid Oral Potassium Tablets/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) |
K-TAB ER, KLOR-CON 10, KLOR-CON 8, KLOR-CON M10, KLOR-CON M15, KLOR-CON M20, POTASSIUM CHLORIDE, POTASSIUM CITRATE ER, UROCIT-K |
| Solid Oral Potassium Capsules/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. The lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) |
POTASSIUM CHLORIDE |
| Clozapine/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) These effects may be compounded by concurrent use of anticholinergic agents.(1-6) CLINICAL EFFECTS: Concurrent use of clozapine with other anticholinergic agents may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6) PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5) PATIENT MANAGEMENT: Avoid the use of other anticholinergic agents with clozapine.(1-6) If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for other anticholinergic agents. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2) DISCUSSION: In a prospective cohort study of 26,720 schizophrenic patients in the Danish Central Psychiatric Research Registry, the odds ratio (OR) for ileus was 1.99 with clozapine and 1.48 with anticholinergics. The OR for fatal ileus was 6.73 with clozapine and 5.88 with anticholinergics. Use of anticholinergics with 1st generation antipsychotics (FGA) increased the risk of ileus compare to FGA alone, but this analysis was not done with clozapine.(5) A retrospective cohort study of 24,970 schizophrenic patients from the Taiwanese National Health Insurance Research Database found that the hazard ratio (HR) for clozapine-induced constipation increased from 1.64 when clozapine is used alone, to 2.15 when used concomitantly with anticholinergics. However, there was no significant difference in the HR for ileus when clozapine is used with and without anticholinergics (1.95 and 2.02, respectively).(6) In the French Pharmacovigilance Database, 7 of 38 cases of antipsychotic-associated ischemic colitis or intestinal necrosis involved clozapine, and 5 of these cases involved use of concomitant anticholinergic agents. Three patients died, one of whom was on concomitant anticholinergics.(3) In a case series, 4 of 9 cases of fatal clozapine-associated GI dysfunction involved concurrent anticholinergic agents.(4) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Zonisamide/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Zonisamide can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of zonisamide with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The UK and US manufacturers of zonisamide state that caution should be used in adults when zonisamide is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity.(1-2) Pediatric and adolescent patients must not take anticholinergic agents (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment and resulted in death.(1) |
ZONEGRAN, ZONISADE, ZONISAMIDE |
| Eluxadoline/Anticholinergics; Opioids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eluxadoline is a mixed mu-opioid and kappa-opioid agonist and delta-opioid antagonist and may alter or slow down gastrointestinal transit.(1) CLINICAL EFFECTS: Constipation related adverse events that sometimes required hospitalization have been reported, including the development of intestinal obstruction, intestinal perforation, and fecal impaction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid use with other drugs that may cause constipation. If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(1) Instruct patients to stop eluxadoline and immediately contact their healthcare provider if they experience severe constipation. Loperamide may be used occasionally for acute management of severe diarrhea, but must be discontinued if constipation develops.(1) DISCUSSION: In phase 3 clinical trials, constipation was the most commonly reported adverse reaction (8%). Approximately 50% of constipation events occurred within the first 2 weeks of treatment while the majority occurred within the first 3 months of therapy. Rates of severe constipation were less than 1% in patients receiving eluxadoline doses of 75 mg and 100 mg.(1) |
VIBERZI |
| Glucagon (Diagnostic)/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility.(1) CLINICAL EFFECTS: Concurrent use of glucagon with anticholinergic agents may increase the risk of gastrointestinal hypomotility, including constipation and bowel complications.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of glucagon as a diagnotic aid is not recommended with the use of anticholinergic agents.(1) If concurrent use is necessary, evaluate the patient's bowel function. Monitor for symptoms of constipation and gastrointestinal hypomotility. DISCUSSION: Both glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility and increase the risk of gastrointestinal adverse effects.(1) |
GLUCAGON HCL |
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Topiramate/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Topiramate can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of topiramate with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The manufacturer of topiramate states that caution should be used when topiramate is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment.(1) A 64-year old woman developed non-exertional hyperthemia while taking multiple psychiatric medications with topiramate.(2) |
EPRONTIA, QSYMIA, QUDEXY XR, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TROKENDI XR |
The following contraindication information is available for UNISOM (DOXYLAMINE) (doxylamine succinate):
Drug contraindication overview.
Doxylamine succinate is contraindicated in patients with known hypersensitivity to doxylamine, other ethanolamine derivative antihistamines, or any ingredient in the formulation. Doxylamine in fixed combination with pyridoxine is contraindicated in patients receiving monoamine oxidase (MAO) inhibitors.
Doxylamine succinate is contraindicated in patients with known hypersensitivity to doxylamine, other ethanolamine derivative antihistamines, or any ingredient in the formulation. Doxylamine in fixed combination with pyridoxine is contraindicated in patients receiving monoamine oxidase (MAO) inhibitors.
There are 0 contraindications.
There are 6 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Angle-closure glaucoma |
| Benign prostatic hyperplasia |
| Bladder outflow obstruction |
| Chronic idiopathic constipation |
| Stenosing peptic ulcer |
| Urinary retention |
There are 3 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Hypertension |
| Hyperthyroidism |
| Ocular hypertension |
The following adverse reaction information is available for UNISOM (DOXYLAMINE) (doxylamine succinate):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 8 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Anaphylaxis Blood dyscrasias Extrasystoles Hallucinations Hemolytic anemia Hypersensitivity drug reaction Hypotension Seizure disorder |
There are 52 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anticholinergic toxicity Dizziness Drowsy Thick bronchial secretions |
| Rare/Very Rare |
|---|
|
Abdominal distension Accidental fall Acute abdominal pain Acute cognitive impairment Agitation Anorexia Ataxia Blurred vision Chest discomfort Chills Constipation Diarrhea Diplopia Dry nose Dry throat Dyspnea Dysuria Euphoria Excitement Fatigue Headache disorder Hyperhidrosis Insomnia Irritability Maculopapular rash Malaise Migraine Nausea Nervousness Nightmares Palpitations Paresthesia Pruritus of skin Skin photosensitivity Skin rash Symptoms of anxiety Tachycardia Tinnitus Tremor Urinary retention Urticaria Vertigo Visual changes Vomiting Wheezing Xerostomia |
The following precautions are available for UNISOM (DOXYLAMINE) (doxylamine succinate):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Contraindicated
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| Doxylamine | 1 Day – 29 Days | CNS excitation and convulsion risk in newborns. |
Contraindicated
| Doxylamine | 30 Days – 2 Years | CNS depression and paradoxical excitation. Avoid use with age <2 years. |
Contraindicated
| Doxylamine (Sedative_Hypnotic) | 2 Years – 12 Years | Avoid use age < 12 years as a sleep aid. Risk of paradoxical CNS stimulation. |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Doxylamine succinate in fixed combination with pyridoxine hydrochloride is intended for use in the management of nausea and vomiting of pregnancy. Numerous epidemiologic studies (including cohort studies, case-control studies, and meta-analyses) have been performed to investigate possible teratogenic effects of doxylamine in fixed combination with pyridoxine in pregnant women. 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 doxylamine succinate and pyridoxine hydrochloride in fixed combination, with or without dicyclomine hydrochloride (a drug included in a combination product that was previously commercially available for nausea and vomiting of pregnancy).
Another meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no clinically important associations between fetal abnormalities and first trimester exposure to doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride. A reanalysis of data from another meta-analysis supporting the safety of doxylamine during pregnancy found that the strength of the data had been overstated, both in terms of the numbers of patients exposed to doxylamine succinate and the reported odds ratio, which suggested a potential protective effect of antihistamines with regard to fetal malformations. However, the reanalysis did not find evidence of an increased risk of fetal malformations associated with doxylamine use.
Historically, there was considerable controversy regarding the teratogenic potential, if any, of doxylamine; however, after evaluating extensive data and information concerning the possible teratogenicity of the drug, FDA concluded that it is unlikely that doxylamine is teratogenic. FDA recognized, however, that despite the large number of pregnancies evaluated to date the possibility that doxylamine may be weakly teratogenic cannot be excluded. Doxylamine was commercially available in the US for the treatment of nausea and vomiting associated with pregnancy in combination with dicyclomine and pyridoxine until 1976, and then in combination with only pyridoxine until 1983 when the manufacturer voluntarily discontinued manufacturing and distributing the combination.
FDA stated that the removal of products containing doxylamine and pyridoxine that previously were commercially available for the management of nausea and vomiting of pregnancy was not for reasons of safety or effectiveness. Most epidemiologic studies (case-control and cohort) in which fixed combinations of doxylamine and pyridoxine with or without dicyclomine were used during pregnancy indicate that an association between use of these combinations and adverse fetal effects does not appear to exist. In a few studies, a weak association between use of the fixed combinations during pregnancy and specific fetal abnormalities (e.g., pyloric stenosis, cardiac defects, oral clefts) was reported, but a causal relationship with the drugs was not established and these findings have not been confirmed by many other studies.
Women considering self-medication with doxylamine during pregnancy should consult a health professional for advice regarding the relative risks and benefits of such therapy. Most reproduction studies in various animal species using doxylamine and pyridoxine alone or in fixed combination have not revealed evidence of harm to the fetus. Studies in rats and mice using doxylamine succinate dosages up to 125 times the maximum human dosage did not reveal evidence of observable congenital abnormalities, but wavy ribs and diaphragmatic hernias occurred in rats at dosages 125-375 times the maximum human dosage; an overall increase in fetal wastage, varying from zero to threefold, occurred in most rodents receiving dosages 125 or more times greater than the maximum human dosage.
Once daily administration of doxylamine succinate and pyridoxine hydrochloride in pregnant rats during organogenesis (gestational day 6-15) resulted in increased fetal resorptions, decreased fetal body weight, and increased skeletal variations with reduced ossification at dosages 60-100 times the highest clinical dosage based on body surface area. In a study in pregnant cynomolgus monkeys receiving doxylamine succinate and pyridoxine hydrochloride once daily during organogenesis (gestational day 22-50) at dosages up to 3.2 times the highest proposed clinical dosage based on body surface area, there were no observed malformations and no evidence of embryo, fetal, or maternal toxicity.
In another study in pregnant cynomolgus and rhesus monkeys and baboons receiving doxylamine succinate and pyridoxine hydrochloride at dosages 0.5-20 times higher than the clinical dosage based on body surface area, ventricular septal defects were observed in preterm (gestational day 100) fetuses; no relationship between dosage and incidence of ventricular septal defects was observed, and no ventricular septal defects were observed in infant monkeys at term. In addition, no ventricular septal defects were observed at gestational day 100 in cynomolgus monkeys administered the combination of doxylamine succinate and pyridoxine hydrochloride for 4-day periods between 22 and 41 days of gestation.
In a small study in monkeys receiving a fixed combination of doxylamine succinate and pyridoxine hydrochloride throughout fetal organogenesis at dosages 10-20 times the maximum human dosage, intraventricular septal defects were present in 4 of 7 fetuses delivered on day 100 of gestation (full-term gestation is about 160 days), while 2 fetuses aborted on the 46th and 56th day of gestation appeared to be developing normally and 3 other fetuses allowed to develop to term were normal. The importance of septal defects in these monkeys is not known, since an opening in the septum is usually present early during fetal development in monkeys. In other studies in monkeys receiving the fixed combination for shorter periods of time, there was no evidence of fetal toxicity.
Another meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no clinically important associations between fetal abnormalities and first trimester exposure to doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride. A reanalysis of data from another meta-analysis supporting the safety of doxylamine during pregnancy found that the strength of the data had been overstated, both in terms of the numbers of patients exposed to doxylamine succinate and the reported odds ratio, which suggested a potential protective effect of antihistamines with regard to fetal malformations. However, the reanalysis did not find evidence of an increased risk of fetal malformations associated with doxylamine use.
Historically, there was considerable controversy regarding the teratogenic potential, if any, of doxylamine; however, after evaluating extensive data and information concerning the possible teratogenicity of the drug, FDA concluded that it is unlikely that doxylamine is teratogenic. FDA recognized, however, that despite the large number of pregnancies evaluated to date the possibility that doxylamine may be weakly teratogenic cannot be excluded. Doxylamine was commercially available in the US for the treatment of nausea and vomiting associated with pregnancy in combination with dicyclomine and pyridoxine until 1976, and then in combination with only pyridoxine until 1983 when the manufacturer voluntarily discontinued manufacturing and distributing the combination.
FDA stated that the removal of products containing doxylamine and pyridoxine that previously were commercially available for the management of nausea and vomiting of pregnancy was not for reasons of safety or effectiveness. Most epidemiologic studies (case-control and cohort) in which fixed combinations of doxylamine and pyridoxine with or without dicyclomine were used during pregnancy indicate that an association between use of these combinations and adverse fetal effects does not appear to exist. In a few studies, a weak association between use of the fixed combinations during pregnancy and specific fetal abnormalities (e.g., pyloric stenosis, cardiac defects, oral clefts) was reported, but a causal relationship with the drugs was not established and these findings have not been confirmed by many other studies.
Women considering self-medication with doxylamine during pregnancy should consult a health professional for advice regarding the relative risks and benefits of such therapy. Most reproduction studies in various animal species using doxylamine and pyridoxine alone or in fixed combination have not revealed evidence of harm to the fetus. Studies in rats and mice using doxylamine succinate dosages up to 125 times the maximum human dosage did not reveal evidence of observable congenital abnormalities, but wavy ribs and diaphragmatic hernias occurred in rats at dosages 125-375 times the maximum human dosage; an overall increase in fetal wastage, varying from zero to threefold, occurred in most rodents receiving dosages 125 or more times greater than the maximum human dosage.
Once daily administration of doxylamine succinate and pyridoxine hydrochloride in pregnant rats during organogenesis (gestational day 6-15) resulted in increased fetal resorptions, decreased fetal body weight, and increased skeletal variations with reduced ossification at dosages 60-100 times the highest clinical dosage based on body surface area. In a study in pregnant cynomolgus monkeys receiving doxylamine succinate and pyridoxine hydrochloride once daily during organogenesis (gestational day 22-50) at dosages up to 3.2 times the highest proposed clinical dosage based on body surface area, there were no observed malformations and no evidence of embryo, fetal, or maternal toxicity.
In another study in pregnant cynomolgus and rhesus monkeys and baboons receiving doxylamine succinate and pyridoxine hydrochloride at dosages 0.5-20 times higher than the clinical dosage based on body surface area, ventricular septal defects were observed in preterm (gestational day 100) fetuses; no relationship between dosage and incidence of ventricular septal defects was observed, and no ventricular septal defects were observed in infant monkeys at term. In addition, no ventricular septal defects were observed at gestational day 100 in cynomolgus monkeys administered the combination of doxylamine succinate and pyridoxine hydrochloride for 4-day periods between 22 and 41 days of gestation.
In a small study in monkeys receiving a fixed combination of doxylamine succinate and pyridoxine hydrochloride throughout fetal organogenesis at dosages 10-20 times the maximum human dosage, intraventricular septal defects were present in 4 of 7 fetuses delivered on day 100 of gestation (full-term gestation is about 160 days), while 2 fetuses aborted on the 46th and 56th day of gestation appeared to be developing normally and 3 other fetuses allowed to develop to term were normal. The importance of septal defects in these monkeys is not known, since an opening in the septum is usually present early during fetal development in monkeys. In other studies in monkeys receiving the fixed combination for shorter periods of time, there was no evidence of fetal toxicity.
| Drug/Drug Class | Severity | Precaution Description | Pregnancy Category Description |
|---|---|---|---|
| Doxylamine | 2 | Compatible per briggs;Overwhelming human and animal data suggests compatibility | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
Doxylamine succinate is expected to be distributed into human milk, because of its low molecular weight. Adverse effects (e.g., excitement, irritability, and sedation) have been reported in infants presumably exposed to doxylamine through human milk. Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of doxylamine.
Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or doxylamine, taking into account the importance of the drug to the woman. The manufacturer of doxylamine/pyridoxine in fixed combination states that this preparation should notbe used in nursing women.
Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.
Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or doxylamine, taking into account the importance of the drug to the woman. The manufacturer of doxylamine/pyridoxine in fixed combination states that this preparation should notbe used in nursing women.
Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.
| Drug Name | Excretion Potential | Effect on Infant | Notes |
|---|---|---|---|
| Doxylamine | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Low molec wt. possible excretion; not recom; may cause paradoxical excitation |
No enhanced Geriatric Use information available for this drug.
Precaution Exists
Geriatric management or monitoring precaution exists.
Precaution Exists
Geriatric management or monitoring precaution exists.
| Drug Name | Narrative | REN | HEP | CARDIO | NEURO | PULM | ENDO |
|---|---|---|---|---|---|---|---|
| Doxylamine | Neuro/Psych-Anticholinergic effects may cause sedation, worsen cognitive impairment and increase fall risk. Non-sedating antihistamine preferred. Gastrointestinal-May cause or worsen pre-existing constipation. Genitourinary-Best avoided in patients with urinary retention from any cause. | N | N | N | Y | N | N |
The following prioritized warning is available for UNISOM (DOXYLAMINE) (doxylamine succinate):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for UNISOM (DOXYLAMINE) (doxylamine succinate)'s list of indications:
| Allergic conjunctivitis | |
| H10.1 | Acute atopic conjunctivitis |
| H10.10 | Acute atopic conjunctivitis, unspecified eye |
| H10.11 | Acute atopic conjunctivitis, right eye |
| H10.12 | Acute atopic conjunctivitis, left eye |
| H10.13 | Acute atopic conjunctivitis, bilateral |
| H10.44 | Vernal conjunctivitis |
| H10.45 | Other chronic allergic conjunctivitis |
| H16.26 | Vernal keratoconjunctivitis, with limbar and corneal involvement |
| H16.261 | Vernal keratoconjunctivitis, with limbar and corneal involvement, right eye |
| H16.262 | Vernal keratoconjunctivitis, with limbar and corneal involvement, left eye |
| H16.263 | Vernal keratoconjunctivitis, with limbar and corneal involvement, bilateral |
| H16.269 | Vernal keratoconjunctivitis, with limbar and corneal involvement, unspecified eye |
| Allergic rhinitis | |
| J30.1 | Allergic rhinitis due to pollen |
| J30.2 | Other seasonal allergic rhinitis |
| J30.5 | Allergic rhinitis due to food |
| J30.8 | Other allergic rhinitis |
| J30.81 | Allergic rhinitis due to animal (cat) (dog) hair and dander |
| J30.89 | Other allergic rhinitis |
| J30.9 | Allergic rhinitis, unspecified |
| Dermatographic urticaria | |
| L50.3 | Dermatographic urticaria |
| Nasal congestion | |
| R09.81 | Nasal congestion |
| Pruritus of skin | |
| L29.8 | Other pruritus |
| L29.81 | Cholestatic pruritus |
| L29.89 | Other pruritus |
| L29.9 | Pruritus, unspecified |
| Rhinorrhea | |
| R09.82 | Postnasal drip |
| Sneezing | |
| R06.7 | Sneezing |
| Urticaria | |
| L50 | Urticaria |
| L50.0 | Allergic urticaria |
| L50.1 | Idiopathic urticaria |
| L50.2 | Urticaria due to cold and heat |
| L50.3 | Dermatographic urticaria |
| L50.4 | Vibratory urticaria |
| L50.5 | Cholinergic urticaria |
| L50.6 | Contact urticaria |
| L50.8 | Other urticaria |
| L50.9 | Urticaria, unspecified |
| L56.3 | Solar urticaria |
| O26.86 | Pruritic urticarial papules and plaques of pregnancy (PUPPp) |
Formulary Reference Tool