Sinequan 10mg/ml Concentrate 120ml

Doxepin is a tricyclic antidepressant (TCA) that primarily inhibits the reuptake of norepinephrine (NE) and serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing the concentration of these neurotransmitters in the synaptic cleft. It also possesses significant antagonistic activity at histamine H1, alpha-1 adrenergic, muscarinic cholinergic, and 5-HT2 receptors, which contribute to its sedative, anticholinergic, and hypotensive effects.

Urgent Side Effects: Seek Medical Attention Immediately

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high or low blood pressure, including:
+ Severe headache
+ Dizziness
+ Passing out
+ Changes in eyesight
Fast heartbeat
Difficulty urinating
Feeling extremely nervous or excitable
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling very tired or weak
Yellowing of the skin or eyes (jaundice)
Ringing in the ears (tinnitus)
Changes in sex interest
Enlarged breasts or nipple discharge
Swelling of the testicles

Important Warning for Asthma Patients

If you have asthma, use this medication with caution. Worsening of asthma has been reported in people taking this medication. If your asthma symptoms worsen while taking this medication, contact your doctor right away.

Other Possible Side Effects

Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. However, if you notice any of the following side effects or if they bother you or do not go away, contact your doctor or seek medical help:

Feeling dizzy, sleepy, tired, or weak
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Dry mouth
Changes in taste
Mouth irritation or mouth sores
Weight gain
Excessive sweating
Flushing
Hair loss
Headache

Reporting Side Effects

This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances. Describe the allergic reaction you experienced, including any symptoms.
Certain health conditions, such as:
+ Difficulty urinating
+ Glaucoma
Current or recent use of specific medications, including:
+ Linezolid or methylene blue
+ Certain antidepressants or Parkinson's disease medications taken within the last 14 days, such as:
- Isocarboxazid
- Phenelzine
- Tranylcypromine
- Selegiline
- Rasagiline (note: taking these medications with this drug can lead to very high blood pressure)
Use of other medications that can cause drowsiness, as combining them with this medication may increase the risk of excessive sleepiness. If you are unsure, consult your doctor or pharmacist.
* Breastfeeding status: do not breastfeed while taking this medication.

This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.

Important Information About Your Medication

It is crucial that you inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

Caution with Daily Activities
Until you understand how this medication affects you, avoid driving and engaging in other activities that require your full attention.

Full Effects and Stopping the Medication
Please note that it may take several weeks to experience the full effects of this medication. Do not stop taking this medication abruptly without consulting your doctor, as this may increase your risk of side effects. If you need to stop taking this medication, your doctor will guide you on how to gradually discontinue it.

Interactions with Other Substances
Avoid consuming alcohol while taking this medication. Before using marijuana, other forms of cannabis, or prescription and over-the-counter drugs that may cause drowsiness, discuss the potential risks with your doctor.

Eye Problems
Some individuals may be at a higher risk of developing eye problems while taking this medication. Your doctor may recommend an eye exam to assess your risk. If you experience eye pain, changes in vision, or swelling and redness around the eye, contact your doctor immediately.

Sun Sensitivity
This medication may increase your susceptibility to sunburn. Exercise caution when spending time outdoors, and inform your doctor if you experience excessive sunburn.

Blood Sugar Monitoring
If you have diabetes, it is essential to closely monitor your blood sugar levels. Be aware of signs of high or low blood sugar, such as:
- Breath that smells like fruit
- Dizziness
- Fast breathing
- Fast heartbeat
- Feeling confused or sleepy
- Feeling weak
- Flushing
- Headache
- Unusual thirst or hunger
- Frequent urination
- Shaking or sweating
Inform your doctor if you experience any of these symptoms.

Special Considerations for Older Adults
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.

Fertility and Pregnancy
Some medications can affect fertility, potentially impacting your ability to have children. If you have concerns, discuss them with your doctor.

Pregnancy and Breastfeeding
If you are pregnant or plan to become pregnant, consult your doctor to weigh the benefits and risks of taking this medication. Taking this medication during the third trimester of pregnancy may pose health risks to the newborn, so it is essential to discuss this with your doctor.

• Monoamine Oxidase Inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine, selegiline, linezolid, methylene blue) - risk of serotonin syndrome, hyperpyretic crises, convulsions, and death. Allow at least 14 days between discontinuing MAOI and starting doxepin, and vice versa.
• Cisapride (risk of QT prolongation and arrhythmias)
• Patients with narrow-angle glaucoma or urinary retention (due to anticholinergic effects)

• CNS Depressants (e.g., alcohol, benzodiazepines, opioids, sedatives, hypnotics, antihistamines) - additive CNS depression, respiratory depression, profound sedation, coma.
• Anticholinergics (e.g., atropine, benztropine, diphenhydramine, oxybutynin) - additive anticholinergic effects (e.g., severe constipation, urinary retention, blurred vision, delirium).
• Sympathomimetics (e.g., epinephrine, norepinephrine, phenylephrine) - enhanced pressor response, risk of arrhythmias and hypertension.
• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine, quinidine, bupropion) - increased plasma concentrations of doxepin and desmethyldoxepin, leading to increased risk of adverse effects.
• Thyroid Hormones - increased risk of cardiac arrhythmias and toxicity.
• Antihypertensives (e.g., guanethidine, clonidine, reserpine) - may antagonize the antihypertensive effects; orthostatic hypotension may be exacerbated.
• QT-prolonging drugs (e.g., antiarrhythmics, antipsychotics, macrolide antibiotics, fluoroquinolones) - increased risk of QT prolongation and torsades de pointes.

• Cimetidine - inhibits doxepin metabolism, leading to increased plasma levels.
• Oral Anticoagulants (e.g., warfarin) - may alter anticoagulant effects, monitor INR.
• Barbiturates - may decrease doxepin plasma levels due to enzyme induction.
• Tobacco Smoking - may decrease doxepin plasma levels due to enzyme induction (CYP1A2).

• Not readily categorized as minor due to the broad interaction profile of TCAs; most interactions are clinically significant.

• Worsening depression
• Suicidal thoughts or behavior
• Unusual changes in behavior (e.g., agitation, irritability, anxiety, panic attacks, insomnia, aggressiveness, impulsivity, akathisia, hypomania, mania)
• Cardiac symptoms (e.g., palpitations, dizziness, syncope)
• Severe constipation or urinary retention
• Blurred vision or eye pain
• Confusion or delirium (especially in elderly)
• Seizures
• Fever, sore throat, or other signs of infection (suggesting blood dyscrasias)

Doxepin is Pregnancy Category C. Use during pregnancy should only be considered if the potential benefit justifies the potential risk to the fetus. Neonates exposed to TCAs in the third trimester have developed withdrawal symptoms (e.g., respiratory distress, feeding difficulties, tremor, hypertonia, seizures).

Doxepin and its active metabolite, desmethyldoxepin, are excreted into breast milk. The American Academy of Pediatrics considers doxepin to be a drug for which the effect on the nursing infant is unknown but may be of concern. Use with caution; monitor infant for sedation, poor feeding, and weight gain. Lower doses may pose less risk.

Not approved for depression or anxiety in pediatric patients. Black Box Warning for increased risk of suicidality in children, adolescents, and young adults. Use for insomnia is off-label and generally reserved for specific cases at very low doses, with careful risk-benefit assessment.

Use with extreme caution due to increased sensitivity to anticholinergic effects (e.g., confusion, delirium, urinary retention, constipation), orthostatic hypotension, and sedation. Elderly patients are more prone to falls. Doxepin is on the Beers Criteria list as a potentially inappropriate medication in older adults due to its strong anticholinergic properties and risk of orthostatic hypotension. Start with lower doses and titrate slowly.

• Doxepin is a potent H1 antagonist, making it highly sedating. This property is leveraged for its use in insomnia at very low doses (3-6 mg).
• The oral concentrate form (10 mg/ml) allows for flexible and precise dosing, especially for low-dose insomnia treatment or careful titration in sensitive patients.
• Due to its anticholinergic and alpha-1 adrenergic blocking effects, doxepin can cause significant dry mouth, constipation, urinary retention, blurred vision, and orthostatic hypotension.
• Cardiac conduction abnormalities (e.g., QT prolongation, QRS widening) are a concern, especially at higher doses or in patients with pre-existing cardiac disease; baseline ECG is recommended.
• Withdrawal symptoms (e.g., nausea, headache, malaise, flu-like symptoms, sleep disturbance, irritability) can occur upon abrupt discontinuation, especially after prolonged use. Taper slowly.
• Therapeutic drug monitoring (TDM) may be useful in cases of non-response, suspected toxicity, or significant drug interactions, aiming for combined doxepin and desmethyldoxepin levels of 100-250 ng/mL for antidepressant effects.

• For Depression/Anxiety: SSRIs (e.g., fluoxetine, sertraline, escitalopram), SNRIs (e.g., venlafaxine, duloxetine), other TCAs (e.g., amitriptyline, imipramine, nortriptyline), atypical antidepressants (e.g., bupropion, mirtazapine).
• For Insomnia: Non-benzodiazepine hypnotics (e.g., zolpidem, eszopiclone, zaleplon), benzodiazepines (e.g., temazepam, lorazepam), melatonin receptor agonists (e.g., ramelteon), antihistamines (e.g., diphenhydramine), trazodone, cognitive behavioral therapy for insomnia (CBT-I).

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.