Promethazine and zoloft (Possible interactions)

In this blog, we are going to talk about the possible interactions between promethazine and zoloft. These two drugs are often used and the safety of every other drug with the use of antidepressants is a major concern. 

This blog will cover the benefits and dangers of taking zoloft with promethazine (Phenergan). 

Is there any interaction between promethazine and zoloft? 

The use of promethazine (Phenergan) and sertraline (zoloft) together can cause extreme drowsiness that could last much longer than the drowsiness caused by each drug individually. 

Studies show that both of these drugs can increase sedation and cause brain fog when used together, especially at high doses. Promethazine is normally prescribed to treat allergic reactions, nausea and as an adjunct in the treatment of insomnia. 

It works by blocking histamine-1 (H1) receptors, which are responsible for producing an allergic reaction in your body. Antihistamines are known for causing sedation as the inhibition of H1 receptors generates the state of drowsiness. 

Zoloft, on the other hand, is an antidepressant. It works for blocking serotonin transporters (SERT) and inhibits the reuptake of leftover serotonin, which increases the amount of this excitatory neurotransmitter to produce its effects. 

Zoloft produces a variety of side effects, one of which include dizziness as well. This is why the use of these two agents can increase the intensity of dizziness. Another possible interaction is related to the cardiovascular system. 

Research indicates that zoloft can cause irregular heart rhythms and can slow down your heart rate. Promethazine, on the other hand, blocks H1 as well as acetylcholine receptors which normally cause vasodilation (widening of blood vessels). 

The inhibition of these receptors leads to vasoconstriction (narrowing of blood vessels) and increases the workload of the heart. These effects, combined with the effects of zoloft, can cause life threatening arrhythmia or irregular heartbeat. 

The data from several case studies indicate that this effect has been deadly in the past for children. It is extremely important to rule out drug interactions. They are often neglected and can be deadly. 

Another possible interaction could relate to the central nervous system (CNS). Although it causes sedation in adults, studies show that this sedation can be followed by unusual excitement and abnormally spiked energy levels. 

This effect is very pronounced in children which is associated with side effects like confusion, excitement, convulsions and sometimes hallucinations. 

Now this indicates that promethazine, at some level, can alter the amount of chemicals in your brain by both inhibiting and stimulating them. 

This effect can interfere with the mechanism of zoloft, by either counteracting or enhancing its effects. This effect can vary from person to person and depends heavily on the condition of a person and the dose of the two drugs. 

Overdose of promethazine and zoloft

If we talk about overdose of promethazine and zoloft, it leads to an extremely life-threatening condition. The overdose of each of these meds individually could be deadly, so you can imagine how dreadful overdose of this combination would be. Following symptoms are expected:

  • Extreme hypo or hypertension, resulting in severe arrhythmia. It could lead to cardiac failure. 
  • Severe allergic reaction leading to respiratory depression associated with tightness of chest, inability to breathe, severe chest pain, wheezing etc. 
  • Skin allergies are also common, with symptoms like redness of skin, painful pus-filled blisters, blue-purple patches, burning sensation etc. 
  • Extreme CNS effects including seizures, confusion, hallucinations, delirium, dementia, abnormal manic behaviour etc. 
  • Extrapyramidal side effects can occur. The incidence depends on the severity of the patient’s pre-existing mental health condition. 

Promethazine and zoloft should not be used in children under 5 years of age and should be used with caution in children older than that. 

The dose should be properly calculated and adjusted for the paediatric population. The combination of promethazine and zoloft should never be used in children. This could result in deadly interactions.

Side effects of promethazine 

Common side effects of promethazine include:

  • Drowsiness/Sedation
  • Dizziness 
  • Confusion
  • Xerostomia/Dry mouth 
  • Poor sleep quality
  • Nightmares
  • Tinnitus 
  • Nausea
  • Vomiting 
  • Constipation 
  • Unusual excitement 
  • Nervousness
  • Itching
  • Impaired motor coordination 

Promethazine can cause serious and potentially life-threatening side effects, especially at higher doses. These include:

  • Respiratory depression, which could be deadly in patients who already have compromised respiratory functions, including people with asthma, chronic obstructive pulmonary disease (COPD), emphysema etc. 
  • Muscle stiffness or paralysis
  • Venous thrombosis, muscle injury, necrosis or gangrene on the site of injection, followed by intravenous administration of promethazine. 
  • Hallucinations
  • Convulsions 
  • Abnormal eye movement 
  • Inability to recognise surroundings or people
  • Swelling in different parts of the body, including tongue, mouth and throat muscles, which result in difficulty in speaking and swallowing. 

Side effects of zoloft 

Common side effects of zoloft include:

  • Loss of appetite
  • Tiredness
  • Feeling angry or agitated
  • Weight gain
  • Inability to digest food
  • Nausea
  • Diarrhoea
  • Loss of libido
  • Sweating/Night sweats
  • Tremors or shaking
  • Insomnia
  • Decreased sex drive
  • Impotence
  • Inability to ejaculate

Zoloft, sometimes, causes serious side effects. Consult your healthcare provider as soon as you can if these symptoms occur:

  • Seizure/convulsions
  • Eye pain with vision problems
  • Memory problems/Dementia 
  • Severe weakness and inability to move
  • Skin allergy, which could include Stevens-Johnson. You might notice red, swollen, or blistered skin, with or without fever. 
  • Allergic reactions, like rash, hives are common. It also includes wheezing, difficulty in breathing, tightness in the chest, trouble breathing, swallowing, or swelling of the mouth, face, lips, tongue, or throat. Few of these symptoms indicate anaphylactic shock. 
  • It could cause low sodium levels which can result in psychological symptoms like confusion, agitation, inability to understand surroundings, memory loss etc.
  • It can cause elongation of QT interval, causing increased heartbeat or arrhythmia

The side effects of these drugs individually are pretty disturbing and they both share some of these as well. The concomitant use can result in much pronounced side effects. 


It is not recommended to start using any medication without your doctor’s approval. Antidepressants are meds which are supposed to be taken daily for several months in order to produce satisfactory therapeutic outcomes. 

For some people, it could take up to 5-6 years. There are literally people who have been using antidepressants for 17 to 20  years now. 

During this prolonged course of this, it is impossible not to suffer from other common ailments like common cold or flu, fever, body pain, bacterial or viral infections etc. 

In such cases make sure you thoroughly discuss the use of other medications with your antidepressant. The dose at which you take these meds also have an important role to play. Take care of the following points when you have to take promethazine and zoloft together:

  • Make sure it is safe for you, as per your condition, to use promethazine and zoloft together. 
  • Do not deviate from the dose your doctor has prescribed. Take only once. 
  • If you fail to understand how to use the drug properly or have any other question, ask your doctor or pharmacist.
  • Ask your doctor before taking these two together if you’re pregnant, trying to conceive or if you’re a breastfeeding mother. 
  • In case of overdose, immediately reach out to the hospital. Make sure you properly guide them about how much drug you have taken and when. 
  • Report any problems with bleeding or bruising to your doctor. If you see any unexplained blisters or rashes on your body, or experience any problems with urination, or if you feel changes in your vision, immediately report to your healthcare provider. 
  • Keep the meds away from children and pets. In case of overdose, immediately take them to the hospital. Promethazine and zoloft both can easily become life-threatening for children. 

Drug interactions should be an important consideration before taking two or more medicines together. Yes, drugs in combination are often used to achieve better therapeutic response but this is not the case with every interaction. 

Some drugs are highly incompatible with one another. They often cancel out each other’s effects or antagonise them. Some drugs are so incompatible that they end up changing the entire chemical composition of one another. 

Some interfere with metabolism or bioavailability (the rate and extent at which the active drug moiety enters systemic circulation/blood). This can lead to drug accumulation in different parts of the body. 

It is always advised to inform your healthcare provider of any medicine you take before getting a new prescription. Your doctor will make sure not to prescribe any such drug which might interfere with those you are already taking. 


In this blog, we have talked about the possible interactions between promethazine and zoloft. Several studies indicate increased drowsiness and cardiovascular effects as the most disturbing and dangerous ones.

 This combination is life threatening in children and should be avoided at all costs. They are also capable of causing CNS interactions. Although it causes sedation in adults, studies show that this sedation can be followed by unusual excitement and abnormally spiked energy levels.

This effect is very pronounced in children which is associated with side effects like confusion, excitement, convulsions and sometimes hallucinations. 

FAQs: Promethazine and zoloft

Can I take promethazine with antidepressants?

The use of promethazine (Phenergan) and sertraline (zoloft) together can cause extreme drowsiness that could last much longer than the drowsiness caused by each drug individually. Studies show that both of these drugs can increase sedation and cause brain fog when used together, especially at high doses. 

What medication should not be taken with Zoloft?

  • Monoaminoxidase inhibitors. The concomitant use increases the risk of serotonin syndrome. 
  • Tryptophan rich foods. 
  • Non-steroidal anti-inflammatory drugs (NSAIDS). The combination can increase the risk of bleeding 
  • Pimozide 

Can I take promethazine for anxiety?

Promethazine can induce sleep, reduce pain and can help relieve the symptoms of allergies. This effect can calm you down. 

Why should you not take sertraline at night?

Do not take sertraline at night if it causes insomnia, loss of libido and urinary problems. It’s best to take it in the morning if you suffer from these side effects. 

What can I take for nausea while on Zoloft?

Ask your doctor, even before using any over-the-counter antiemetic drug. Try taking your zoloft with food, which might help you tolerate the drug better and decrease gastrointestinal side effects like nausea and acid reflux. 

Does promethazine help with panic attacks?

Promethazine is not FDA approved for the treatment of panic attacks or anxiety. It also causes several side effects. Make sure you don’t start using any medication without your doctor’s approval. 


Was this helpful?

Thanks for your feedback!