Usage
Doxylamine succinate, a first-generation antihistamine, is primarily prescribed for the short-term management of insomnia, particularly difficulty falling asleep. It is also used, in combination with pyridoxine hydrochloride, for the treatment of nausea and vomiting during pregnancy (NVP) in women who don’t respond to conservative management. It can additionally provide temporary relief from allergy symptoms such as rhinorrhea, sneezing, lacrimation, itchy eyes, and oronasopharyngeal itching associated with allergic rhinitis (hay fever) or other upper respiratory allergies. Its pharmacological classifications include antihistamine, sedative, and antiemetic (when combined with pyridoxine).
Doxylamine’s mechanism of action involves competitive antagonism of histamine H1 receptors. This action reduces the effects of histamine, leading to sedation and relief of allergy symptoms. Its antiemetic effect, when used with pyridoxine, is not fully understood but may involve modulating central and peripheral pathways involved in NVP.
Alternate Names
Doxylamine is often referred to as doxylamine succinate, which specifies the succinate salt form commonly used in medications. Brand names include Unisom SleepTabs, NyQuil, and several store brands for the single-ingredient formulation. For the combination product with pyridoxine, brand names include Diclegis and Bonjesta.
How It Works
Pharmacodynamics: Doxylamine primarily acts as an inverse agonist at the H1 histamine receptor. By binding to and stabilizing the inactive state of the receptor, it reduces histamine’s effects, leading to decreased capillary permeability and smooth muscle contraction, thus relieving allergy symptoms. It also exhibits anticholinergic properties, which contribute to its sedative effects by affecting the central nervous system. The precise mechanism behind its antiemetic effect in combination with pyridoxine is unknown but may involve modulating central neurotransmitter pathways related to nausea and vomiting.
Pharmacokinetics: Doxylamine is well-absorbed orally, reaching peak plasma concentrations within 2 to 4 hours. It is metabolized primarily in the liver via CYP450 enzymes, and the elimination half-life ranges from 8 to 12 hours. Excretion occurs mainly through the kidneys.
Dosage
Standard Dosage
Adults:
- Insomnia: 25 mg orally 30 minutes before bedtime. For some individuals, 12.5 mg may be sufficient, while others might require up to 50 mg. Do not exceed two weeks of continuous use for insomnia.
- Allergic Rhinitis: 12.5 mg orally every 4 to 6 hours, not exceeding 75 mg in 24 hours.
Children:
Doxylamine use should be avoided in children under two years of age due to the potential risk of severe adverse reactions, including cardiopulmonary arrest.
- Ages 2 to <6 years: 1.9–3.125 mg every 4–6 hours, not to exceed 18.75 mg in 24 hours.
- Ages 6 to <12 years: 3.75–6.25 mg every 4–6 hours, not to exceed 37.5 mg in 24 hours.
- Ages 12 years and older: Follow adult dosing guidelines.
Special Cases:
- Elderly Patients: Start with a lower dose (12.5 mg) and adjust cautiously based on response and tolerance due to increased sensitivity to anticholinergic effects and slower drug clearance.
- Patients with Renal Impairment: Dosage adjustment may be necessary depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Reduce the dose as doxylamine is metabolized in the liver.
- Patients with Comorbid Conditions: Caution is advised in patients with glaucoma, urinary retention, prostatic hypertrophy, pyloroduodenal obstruction, cardiovascular disease, hyperthyroidism, or respiratory diseases.
Clinical Use Cases
Doxylamine is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations. Its primary indications are insomnia and NVP. Other antiemetics and sedatives are preferred in these clinical contexts.
Dosage Adjustments
Dose modifications are necessary for elderly patients, and those with renal or hepatic dysfunction. Consider patient-specific factors and monitor closely for adverse effects.
Side Effects
Common Side Effects:
Drowsiness, dizziness, dry mouth, blurred vision, constipation, and urinary retention.
Rare but Serious Side Effects:
Allergic reactions (rash, itching, swelling), confusion, hallucinations, and cardiac arrhythmias.
Long-Term Effects:
Chronic use can lead to tolerance and dependence, especially at higher doses. Cognitive impairment and anticholinergic toxicity are also potential concerns with prolonged use.
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis), agranulocytosis, and paradoxical excitation (especially in children).
Contraindications
Hypersensitivity to doxylamine, narrow-angle glaucoma, urinary retention, severe liver disease, and concurrent use of monoamine oxidase inhibitors (MAOIs).
Drug Interactions
Alcohol, other CNS depressants (benzodiazepines, opioids), anticholinergics, and MAOIs can potentiate doxylamine’s effects. It may also interact with certain medications metabolized by CYP450 enzymes.
Pregnancy and Breastfeeding
Doxylamine is categorized as Pregnancy Category B in the USA for use as a single agent. When combined with pyridoxine, the FDA considers this combination to be Pregnancy Category A. While generally considered safe for use during pregnancy when prescribed for NVP, it’s essential to weigh the potential risks and benefits. Doxylamine is excreted in breast milk; thus, caution is advised during breastfeeding.
Drug Profile Summary
- Mechanism of Action: H1 receptor inverse agonist, anticholinergic.
- Side Effects: Drowsiness, dizziness, dry mouth, blurred vision, constipation, urinary retention.
- Contraindications: Hypersensitivity, narrow-angle glaucoma, urinary retention, severe liver disease, concurrent MAOI use.
- Drug Interactions: Alcohol, CNS depressants, anticholinergics, MAOIs.
- Pregnancy & Breastfeeding: Generally safe for NVP when prescribed, caution advised during breastfeeding.
- Dosage: Adults: 25 mg for insomnia, 12.5 mg every 4–6 hours for allergies. Pediatric dosing varies by age.
- Monitoring Parameters: Mental status, vital signs, and adverse effects.
Popular Combinations
Doxylamine is commonly combined with pyridoxine hydrochloride (vitamin B6) for managing nausea and vomiting during pregnancy.
Precautions
Assess for pre-existing conditions like glaucoma, urinary retention, and liver disease. Exercise caution in elderly patients, pregnant/breastfeeding women, and children. Avoid activities requiring alertness. Alcohol should be avoided while taking doxylamine.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxylamine?
A: Adults: 25 mg for insomnia, 12.5 mg every 4-6 hours for allergies (max 75 mg/24h). Pediatric dosing varies based on age and indication.
Q2: How does Doxylamine work for insomnia?
A: It acts as an H1 receptor inverse agonist, blocking histamine’s effects in the brain, promoting sedation and sleep.
Q3: Can I take Doxylamine with alcohol?
A: No, combining doxylamine with alcohol can intensify drowsiness and other side effects.
Q4: What are the common side effects of Doxylamine?
A: Drowsiness, dry mouth, blurred vision, constipation, and urinary retention.
Q5: Is Doxylamine safe during pregnancy?
A: When combined with pyridoxine, doxylamine is considered Pregnancy Category A by the FDA and is commonly prescribed for NVP.
Q6: Can I take Doxylamine if I have glaucoma?
A: No, doxylamine is contraindicated in patients with narrow-angle glaucoma due to its anticholinergic effects, which can worsen the condition.
Q7: How long can I take Doxylamine for insomnia?
A: Doxylamine should be used for no more than two weeks for insomnia. Consult a healthcare professional if insomnia persists beyond this period.
Q8: What should I do if I experience allergic reactions to Doxylamine?
A: Discontinue the medication immediately and seek medical attention. Symptoms of an allergic reaction may include rash, itching, swelling, difficulty breathing, and dizziness.
Q9: Can Doxylamine be used in children?
A: Yes, but dosing must be adjusted based on age and weight. It should not be used in children under two years old. Consult a healthcare professional for appropriate pediatric dosing.
