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Doxylamine - Uses, Dose, MOA, Side effects, Brands

Doxylamine is an antihistamine medication that is commonly used to treat symptoms of allergies, hay fever, and the common cold. It works by blocking the action of histamine, a substance in the body that causes allergic symptoms. Doxylamine is also known for its sedative effects and is often used as a sleep aid in over-the-counter medications. It is available in various forms, including tablets, capsules, and liquid preparations. However, it's important to use doxylamine cautiously and as directed, as misuse or overuse can lead to side effects such as drowsiness, dizziness, dry mouth, blurred vision, and constipation.

Doxylamine (Sleeping aid) tablets are recommended for the treatment of nausea and vomiting during pregnancy (in combination with pyridoxine). It is a sedative antihistamine and is used for the treatment of insomnia.

Doxylamine Uses:

Insomnia:
- It is used as a sleeping aid to reduce the time to fall asleep.
Off-Label Use of Doxylamine in Adults:
- It is recommended for the treatment of nausea and vomiting during pregnancy.

Doxylamine Adult dose:

Doxylamine Dose in the treatment of Insomnia:

When treating insomnia with doxylamine, the recommended dose is usually 25 milligrams.
You take it by mouth once a day, about 30 minutes before you plan to go to bed.
It's essential to follow the instructions given by your healthcare professional carefully.

Doxylamine Dose in children:

Doxylamine Dose in the treatment of Insomnia:

For children aged 12 years and older, as well as adolescents, the typical dose of doxylamine for treating insomnia is 25 milligrams.
This should be taken orally as a tablet once a day before bedtime, or as directed by a healthcare professional.

Pregnancy risk category: A

The use of doxylamine in combination with pyridoxine during pregnancy has not been found to increase the basic risk of major birth defects.
According to the American College of Obstetricians and Gynecologists (ACOG), doxylamine can be used to treat nausea and vomiting during pregnancy.

Use of Doxylamine while breastfeeding

Doxylamine succinate can likely be passed into breast milk, although the exact amounts are not known.
Breastfeeding infants exposed to doxylamine may experience adverse effects such as unusual excitement, irritability, or sedation.
Infants with respiratory conditions like apnea may be particularly vulnerable.
If a breastfeeding infant is exposed to a first-generation antihistamine like doxylamine through breast milk, it's advisable to monitor them for signs of irritability or drowsiness.

Dose in Kidney disease:

According to the manufacturer's labeling, there are no specific dosage adjustments recommended for individuals with renal impairment when using doxylamine.

Dose in Liver disease:

According to the manufacturer's labeling, there are typically no specific dosage adjustments recommended for individuals with hepatic (liver) impairment when using doxylamine.

Side effects of Doxylamine:

Cardiovascular:
- Palpitations
- Tachycardia
Central Nervous System:
- Disorientation
- Dizziness
- Drowsiness
- Headache
- Paradoxical Central Nervous System Stimulation
- Vertigo
Gastrointestinal:
- Anorexia
- Constipation
- Diarrhea
- Dry Mucous Membranes
- Epigastric Pain
- Xerostomia
Genitourinary:
- Dysuria
- Urinary Retention
Ophthalmic:
- Blurred Vision
- Diplopia

Contraindications to Doxylamine:

In over-the-counter (OTC) labeling, it is typically advised not to use doxylamine in children under 12 years of age. However, in Canadian labeling, additional contraindications exist, which are not present in the US labeling. These include:

Hypersensitivity to doxylamine or any component of the formulation.
Narrow-angle glaucoma.
Asthmatic attack.
Prostatic hypertrophy.
Stenosing peptic ulcer or pyloroduodenal obstruction.
Bladder-neck obstruction.
Concurrent use with monoamine oxidase inhibitors (MAOIs).

These contraindications are important to consider and should be followed according to the specific labeling guidelines in the respective countries.

Warnings and precautions

CNS depression:

Doxylamine may cause CNS depression, affecting physical or mental abilities.
Patients should be cautious when performing tasks requiring mental alertness, like operating machinery or driving.

Sleeplessness

If difficulty sleeping persists for more than two weeks, consult a healthcare provider.

Glaucoma and increased intraocular pressure:

Use doxylamine with caution in patients with increased intraocular pressure or angle-closure glaucoma.

Prostatic hyperplasia, urinary obstruction

Exercise caution when using doxylamine in patients with prostatic hyperplasia (enlarged prostate) or urinary obstruction.

Respiratory disease

Use doxylamine cautiously in patients with asthma or other chronic respiratory conditions.

Doxylamine: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Acetylcholinesterase inhibitors	Anticholinergic Agents may have a decreased therapeutic effect. Anticholinergic Agents can decrease the therapeutic effects of Acetylcholinesterase inhibitors.
Alcohol (Ethyl)	Doxylamine may increase the CNS depressant effects. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with alcohol is not recommended
Alizapride	CNS Depressants may increase the CNS depressant effects.
Amantadine	Anticholinergic Agents may have an enhanced anticholinergic effect.
Amezinium	Amezinium may have a stronger stimulatory effect if it is combined with antihistamines.
Amphetamines	May decrease the sedative effects of Antihistamines.
Anticholinergic Agents	Other Anticholinergic Agents may have an adverse/toxic effect.
Betahistine	Betahistine's therapeutic effects may be diminished by antihistamines.
Botulinum Toxin-Containing Products	Anticholinergic Agents may have an enhanced anticholinergic effect.
Brexanolone	CNS Depressants can increase the CNS depressant effects of Brexanolone.
Brimonidine (Topical)	CNS Depressants may increase the CNS depressant effects.
Bromopride	CNS Depressants may increase the CNS depressant effects.
Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Cannabis	CNS Depressants may increase the CNS depressant effects.
Chloral Betaine	Anticholinergic Agents may have an adverse/toxic effect.
Chlorphenesin Carbamate	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
CNS Depressants	Doxylamine could increase the CNS depressant effects of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dimethindene (Topical).	CNS Depressants may increase the CNS depressant effects.
Dronabinol	CNS Depressants may increase the CNS depressant effects.
Esketamine	CNS Depressants may increase the CNS depressant effects.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents can reduce the therapeutic effects of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic agents may increase the toxic/adverse effects of Glucagon. Particularly, there may be an increase in the likelihood of gastrointestinal adverse reactions.
HydrOXYzine	CNS Depressants may increase the CNS depressant effects.
Itopride	Itopride's therapeutic effects may be diminished by anticholinergic agents.
Kava Kava	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Lofexidine	CNS Depressants may have a greater depressant effect on the brain. Management: Separate drug interaction monographs are available for drugs listed as an exception to this monograph.
Magnesium Sulfate	CNS Depressants may increase the CNS depressant effects.
MetyroSINE	MetyroSINE may have a sedative effect that can be enhanced by CNS depressants.
Mianserin	Anticholinergic Agents may have an enhanced anticholinergic effect.
Minocycline	CNS Depressants may increase the CNS depressant effects.
Mirabegron	Anticholinergic agents may increase the toxic/adverse effects of Mirabegron.
Mirtazapine	CNS Depressants can increase the CNS depressant effects of Mirtazapine.
Monoamine Oxidase Inhibitors	Doxylamine may have an increased anticholinergic activity. Management: The US manufacturer of Diclegis (doxylamine/pyridoxine) and the manufacturers of Canadian doxylamine products specifically lists use with monoamine oxidase inhibitors as contraindicated. Exceptions: Linezolid; Procarbazine; Rasagiline; Safinamide; Selegiline; Tedizolid.
Nabilone	CNS Depressants may increase the CNS depressant effects.
Nitroglycerin	The absorption of Nitroglycerin may be decreased by anticholinergic agents. Anticholinergic Agents may reduce the dissolution sublingual nitroglycerin tablet, which could impair or slow down nitroglycerin absorbtion.
Piribedil	CNS Depressants could increase the CNS depressant effects of Piribedil.
Pitolisant	Antihistamines can reduce the therapeutic effects of Pitolisant.
Pramipexole	Pramipexole may have a greater sedative effect if it is combined with CNS depressants.
Ramosetron	Ramosetron's constipating effects may be enhanced by anticholinergic agents.
ROPINIRole	CNS Depressants can increase the sedative effects of ROPINIRole.
Rotigotine	CNS Depressants can increase the sedative effects of Rotigotine.
Rufinamide	CNS Depressants may have an adverse/toxic effect that can be exacerbated by this. Particularly, dizziness and sleepiness may be increased.
Selective Serotonin Reuptake inhibitors	CNS Depressants can increase the toxic/adverse effects of Selective Serotonin Resuptake Inhibitors. Particularly, psychomotor impairment could be increased.
Tetrahydrocannabinol	CNS Depressants may increase the CNS depressant effects.
Tetrahydrocannabinol, and Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Thiazide and Thiazide - Like Diuretics	Anticholinergic Agents can increase serum Thiazide or Thiazide-Like Diuretics.
Topiramate	Topiramate's toxic/adverse effects may be exacerbated by anticholinergic agents.
Trimeprazine	CNS Depressants may increase the CNS depressant effects.
Risk Factor D (Consider therapy modifications)
BenzylpenicilloylPolylysine	Antihistamines may diminish the diagnostic effect of BenzylpenicilloylPolylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. To assess for persistent antihistaminic effects, a histamine skin test can be performed.
Blonanserin	CNS Depressants can increase the CNS depressant effects of Blonanserin.
Buprenorphine	CNS Depressants can increase the CNS depressant effects of buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Buprenorphine patches (Butrans) should be initiated at 5 mg/hr for adults when taken with other CNS depression drugs.
Chlormethiazole	CNS Depressants may increase the CNS depressant effects. Monitoring: Look out for signs of CNS depression. If a combination of chlormethiazole and other drugs is required, a reduced dose should be used.
Droperidol	CNS Depressants may increase the CNS depressant effects. Management: Droperidol and other CNS agents, such as opioids, may be reduced or used in combination with droperidol. Separate drug interaction monographs provide more detail on exceptions to this monograph.
Flunitrazepam	CNS Depressants can increase the CNS depressant effects of Flunitrazepam.
Hyaluronidase	Hyaluronidase's therapeutic effects may be diminished by antihistamines. Management: Patients who are taking antihistamines, especially at higher doses, may not have the desired clinical response to standard doses hyaluronidase. Higher doses of hyaluronidase might be necessary.
HYDROcodone	CNS Depressants can increase the CNS depressant effects of HYDROcodone. When possible, avoid concomitant use with hydrocodone and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Methotrimeprazine	Methotrimeprazine may have a higher CNS depressant activity than CNS Depressants. Methotrimeprazine can increase the CNS depressant effects of CNS Depressants. Management: Lower the adult dose of CNS Depressants by 50% and start concomitant methotrimeprazine treatment. After clinically proven efficacy of methotrimeprazine, further CNS depressant dose adjustments should only be made.
Opioid Agonists	CNS Depressants can increase the CNS depressant effects of Opioid Aggonists. Management: When possible, avoid concomitant use opioid agonists and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
OxyCODONE	CNS Depressants can increase OxyCODONE's CNS depressant effects. When possible, avoid the simultaneous use of oxycodone and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Perampanel	CNS Depressants may have a greater CNS depressant effect. Perampanel and any other CNS depressant drug should be used in combination. Patients who take perampanel together with other drugs that have CNS depressant activity should not engage in complex or high-risk activities until they are familiar with the combination.
Pramlintide	Anticholinergic Agents may have an enhanced anticholinergic effect. These effects are only for the GI tract.
Secretin	Secretin's therapeutic effects may be diminished by anticholinergic agents. Concomitant use: Secretin and anticholinergic agents should be avoided. Stop using anticholinergic drugs for at least five half-lives before administering secretin.
Sodium Oxybate	CNS Depressants may have a greater depressant effect if taken in combination. Management: Look for alternatives to the combination use. If you must combine use, reduce the doses of any one or more drugs. It is not recommended to combine sodium oxybate and alcohol, or any sedative hypnotics.
Suvorexant	CNS Depressants can increase the CNS depressant effects of Suvorexant. Management: Suvorexant or any other CNS depressionant can be reduced in doses. Suvorexant should not be taken with alcohol. It is also not recommended to take suvorexant along with any other drugs for insomnia.
Tapentadol	CNS Depressants may increase the CNS depressant effects. Tapentadol, benzodiazepines and other CNS depressants should be avoided when possible. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Zolpidem	CNS Depressants can increase the CNS depressant effects of Zolpidem. Management: For men who also take CNS depressants, reduce the adult Intermezzo brand sublingual Zolpidem dose to 1.75mg. For women, no dose adjustment is advised. Avoid using CNS depressants at night; do not use alcohol.
Risk Factor X (Avoid Combination)
Aclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Azelastine (Nasal)	CNS Depressants could increase the CNS depressant effects of Azelastine.
Bromperidol	CNS Depressants may increase the CNS depressant effects.
Cimetropium	Cimetropium may have an anticholinergic effect that can be enhanced by the use of anticholinergic agents.
Eluxadoline	Eluxadoline may cause constipation by using anticholinergic agents.
Glycopyrrolate (Oral Inhalation)	Anticholinergic agents may increase the anticholinergic effects of Glycopyrrolate (Oral inhalation).
Glycopyrronium (Topical)	Anticholinergic Agents may have an enhanced anticholinergic effect.
Oral Inhalation with Ipratropium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Levosulpiride	Anticholinergic Agents can reduce the therapeutic effects of Levosulpiride.
Orphenadrine	Orphenadrine may be more effective against CNS depression than other drugs.
Oxatomide	Anticholinergic Agents may have an enhanced anticholinergic effect.
Oxomemazine	CNS Depressants may increase the CNS depressant effects.
Paraldehyde	Paraldehyde may be enhanced by CNS depressants.
Potassium Chloride	Potassium Chloride may have an ulcerogenic effect that can be exacerbated by anticholinergic agents. Treatment: Patients taking drugs that have significant anticholinergic effects should not consume any oral dose form of potassium chloride.
Potassium Citrate	Potassium Citrate may be more ulcerogenic if it is given to anticholinergic agents.
Revefenacin	Revefenacin may be enhanced by anticholinergic agents.
Thalidomide	CNS Depressants can increase Thalidomide's CNS depressant effects.
Tiotropium	Anticholinergic agents may increase the anticholinergic effects of Tiotropium.
Umeclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.

Monitoring parameters:

None mentioned.

How to administer Doxylamine?

It is administered orally at bedtime or with an evening meal to reduce the gastrointestinal side effects.

Mechanism of action of Doxylamine:

Doxylamine works by competing with histamine for certain receptor sites in the body, specifically the H-receptor sites on effector cells.
It also blocks the chemoreceptor trigger zone, reducing feelings of nausea and vomiting.
Additionally, it decreases vestibular stimulation and dampens the function of the inner ear (labyrinthine function) by acting centrally to inhibit the activity of a neurotransmitter called acetylcholine.

Metabolism: