Usage
- Doxylamine + Vitamin B6 is prescribed for the treatment of nausea and vomiting during pregnancy (NVP) in women who do not respond to conservative management. It is particularly effective for morning sickness.
- Pharmacological classification: Antiemetic, Antihistamine (Doxylamine), Vitamin (B6)
- Mechanism of action: The exact mechanism is not fully understood, but it is thought that doxylamine, an antihistamine, blocks the action of histamine at H1 receptors in the brain, which are involved in the vomiting reflex. Vitamin B6 is thought to play a synergistic role, potentially by affecting neurotransmitters or alleviating a possible B6 deficiency associated with NVP. The extended-release formulation provides prolonged action.
Alternate Names
- Doxylamine succinate + Pyridoxine hydrochloride
- Brand names: Diclegis, Bonjesta, Xonvea, APO-DOXYLAMINE/B6
How It Works
- Pharmacodynamics: Doxylamine, a first-generation antihistamine, acts primarily by antagonizing H1 receptors in the brain, thereby suppressing the chemoreceptor trigger zone (CTZ) and the vomiting center in the medulla oblongata. Vitamin B6’s role in NVP is less clear but it potentially helps restore vitamin B6 levels, which may be deficient in pregnant women experiencing NVP. It may also have independent antiemetic properties.
- Pharmacokinetics: Doxylamine is well-absorbed orally and is metabolized primarily in the liver. It is excreted primarily in the urine. Pyridoxine is readily absorbed from the GI tract and is converted to its active form, pyridoxal 5’-phosphate, in the liver. Excess pyridoxine is excreted in the urine.
- Mode of action: Doxylamine competes with histamine at H1 receptors. Vitamin B6 is a cofactor for numerous enzymes involved in amino acid metabolism.
- Receptor binding: Doxylamine binds to H1 receptors.
- Elimination pathways: Doxylamine is metabolized hepatically and excreted renally. Pyridoxine and its metabolites are excreted primarily in the urine.
Dosage
Standard Dosage
Adults:
- Initial dose: Two 10 mg/10 mg tablets orally at bedtime.
- If symptoms persist, the dose may be increased up to a maximum of four tablets daily (one in the morning, one mid-afternoon, and two at bedtime).
Children:
- Use is not generally recommended for children outside the context of NVP. Doxylamine alone is used for insomnia or allergy symptoms in children over 12 years old, with dosage adjusted based on weight or age. Consult pediatric guidelines for specific recommendations.
Special Cases:
- Elderly Patients: Use with caution due to increased sensitivity to anticholinergic side effects. Dose adjustment may be necessary.
- Patients with Renal Impairment: Caution advised; dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Use with caution, as doxylamine is metabolized in the liver. Dose adjustment may be needed.
- Patients with Comorbid Conditions: Use with caution in patients with asthma, glaucoma, urinary retention, peptic ulcer disease, and pyloroduodenal obstruction.
Clinical Use Cases
- The combination is specifically indicated for NVP and not routinely used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations.
Dosage Adjustments
- Dose adjustments may be needed based on individual response and tolerability. In cases of renal or hepatic impairment, careful consideration and potential dose reduction should be employed.
Side Effects
Common Side Effects
- Drowsiness
- Dry mouth
- Dizziness
- Constipation
- Headache
Rare but Serious Side Effects
- Allergic reactions (rash, itching, hives, swelling)
- Blurred vision, vision changes
- Difficulty urinating
- Fast, irregular heartbeat
- Shortness of breath
- Confusion
- Seizures
Long-Term Effects
- Not typically used long-term outside of pregnancy.
Adverse Drug Reactions (ADR)
- Severe allergic reactions (anaphylaxis)
- Seizures
- Angle-closure glaucoma exacerbation
- Urinary retention
Contraindications
- Hypersensitivity to doxylamine, pyridoxine, or any component of the formulation.
- Concomitant use of monoamine oxidase inhibitors (MAOIs).
- Asthma, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, bladder neck obstruction.
Drug Interactions
- Alcohol and other CNS depressants can potentiate drowsiness.
- Anticholinergic drugs can have additive effects.
- MAOIs are contraindicated due to the risk of prolonged and intensified anticholinergic effects.
- May interact with some medications for bladder problems, stomach problems, travel sickness, and Parkinson’s disease.
Pregnancy and Breastfeeding
- Doxylamine is classified as Pregnancy Category A in Australia and is considered safe for use in pregnancy for NVP.
- Pyridoxine is an essential nutrient during pregnancy.
- While both drugs can be excreted in breast milk, using the combination is generally considered acceptable during breastfeeding, especially given the nutritional importance of Vitamin B6. Consult with a physician to weigh the risks and benefits.
Drug Profile Summary
- Mechanism of Action: Doxylamine: H1 receptor antagonist; Pyridoxine: Vitamin B6 analog; synergistically reduce NVP.
- Side Effects: Drowsiness, dry mouth, dizziness, constipation, blurred vision (rarely seizures, allergic reactions).
- Contraindications: Hypersensitivity, MAOI use, certain pre-existing medical conditions (asthma, glaucoma, urinary retention).
- Drug Interactions: Alcohol, CNS depressants, anticholinergics, MAOIs.
- Pregnancy & Breastfeeding: Generally considered safe for both; consult physician.
- Dosage: Adults: Two tablets at bedtime initially, up to four tablets daily.
- Monitoring Parameters: Monitor for efficacy in reducing NVP and for side effects, especially drowsiness.
Popular Combinations
- This combination itself is a popular and clinically established therapy for NVP. Adding other antiemetics is not usually recommended as first-line treatment.
Precautions
- General Precautions: Assess for hypersensitivity, co-existing conditions, and concomitant medications.
- Pregnant Women: Monitor for efficacy and side effects.
- Breastfeeding Mothers: Monitor infant for potential drowsiness.
- Children & Elderly: Generally not recommended for routine use outside of NVP in pregnancy. Exercise caution in the elderly due to increased sensitivity to anticholinergic effects.
- Lifestyle Considerations: Avoid alcohol and activities requiring mental alertness until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxylamine + Vitamin B6?
A: The initial dose is two 10mg/10mg tablets orally at bedtime. If symptoms persist, the dose may be increased up to a maximum of four tablets per day (one in the morning, one mid-afternoon, and two at bedtime).
Q2: How does this combination work to relieve nausea and vomiting?
A: The exact mechanism is not fully understood, but it is believed that doxylamine blocks histamine receptors in the brain, while vitamin B6 may play a supporting role or potentially address a B6 deficiency.
Q3: Can I take this medication if I am breastfeeding?
A: While both doxylamine and pyridoxine are excreted in breast milk, the combination is generally considered acceptable during breastfeeding. Consult with your physician.
Q4: What are the common side effects?
A: The most common side effects are drowsiness, dry mouth, dizziness, constipation, and headache.
Q5: Are there any serious side effects I should watch out for?
A: Yes, though rare, serious side effects can include allergic reactions, blurred vision, difficulty urinating, rapid heartbeat, shortness of breath, confusion, and seizures. Seek immediate medical attention if these occur.
Q6: Can I drink alcohol while taking this medication?
A: No, alcohol should be avoided as it can exacerbate the drowsiness caused by doxylamine.
Q7: Is it safe to drive while taking this medication?
A: It is advisable to avoid driving or operating machinery until the effects of the medication are known, as it can cause drowsiness.
Q8: Can I crush or chew the tablets?
A: No, the tablets should be swallowed whole. Crushing or chewing them can interfere with the extended-release mechanism and alter drug delivery.
Q9: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose.
Q10: What if conservative management of NVP isn’t effective?
A: If lifestyle modifications and dietary changes do not adequately control NVP, doxylamine + pyridoxine is often the recommended first-line pharmacotherapy.
