Does fluvoxamine interact with venlafaxine? (+1 side effect)

This article will answer the question, ‘Does fluvoxamine interact with venlafaxine?’ We will also discuss the potential side effects associated with the interaction as well as management techniques in case it happens.

Does fluvoxamine interact with venlafaxine?

No, fluvoxamine does not directly interact with venlafaxine. Both of these drugs work through the same mechanism i.e. by blocking the reuptake of serotonin. This can lead to an increase in the levels of serotonin neurotransmitters leading to serotonin syndrome.

Fluvoxamine (Luvox) is an antidepressant that belongs to the class of selective serotonin reuptake inhibitor (SSRI). It is indicated for the treatment of depression and obsessive-compulsive disorder.

Venlafaxine (Effexor) is also an antidepressant belonging to the class of serotonin and norepinephrine reuptake inhibitor (SNRI). It is indicated for the treatment of cataplexy, depression and social anxiety disorder. (1)

What are drug interactions?

Medicines are responsible for making us feel better and improving our condition. Sometimes, drugs can interact with other drugs, health conditions or food and cause problems. Such interactions can lead to serious side effects and sometimes can be fatal.

Drug-drug interactions: When two or more drugs interact with one another. For example, dextromethorphan interacts with venlafaxine.

Drug-food interactions: When a drug interacts with a specific type of food. For example, nifedipine interacts with grapefruit juice.

Drug-condition interactions: A drug reaction can occur when it is given with a specific condition. For example, individuals with high blood pressure should not take decongestants as that will increase the blood pressure more.

What drugs interact with fluvoxamine?

Fluvoxamine can interact with several drugs. Some of the drug classes that interact with fluvoxamine are listed below:

• Monoamine Oxidase inhibitors (MAOIs): Increased risk of serotonin syndrome
• Selective serotonin reuptake inhibitors (SSRIs): Increased risk of serotonin syndrome
• Serotonin and norepinephrine reuptake inhibitors (SNRIs): Increased risk of serotonin syndrome
• Warfarin and anticoagulants: Increased risk of bleeding
• Triptans (used for migraine): Increased risk of serotonin syndrome
• Tricyclic antidepressants (TCAs): Increased risk of serotonin syndrome
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Increased risk of bleeding
• Benzodiazepines: Enhancement of sedative effects
• Antiplatelet drugs: Increased risk of bleeding
• St. John’s Wort: Increased risk of serotonin syndrome 
• Cimetidine: Increase levels of fluvoxamine in blood

What drugs interact with venlafaxine?

Venlafaxine can interact with a variety of drug classes. Some of them are listed below:

• Monoamine Oxidase inhibitors (MAOIs): Increased risk of serotonin syndrome
• Selective serotonin reuptake inhibitors (SSRIs): Increased risk of serotonin syndrome
• Serotonin and norepinephrine reuptake inhibitors (SNRIs): Increased risk of serotonin syndrome:
• Lithium: Increased risk of serotonin syndrome
• Cimetidine: Increase the levels of venlafaxine in blood
• Triptans (Used for migraine): Increased risk of serotonin syndrome
• Tricyclic antidepressants (TCAs): Increased risk of serotonin syndrome
• Linezolid (Antibiotic): Increased risk of serotonin syndrome
• Warfarin and anticoagulants: Increased risk of bleeding
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Increased risk of bleeding

What are the potential side effects of taking fluvoxamine with venlafaxine?

Fluvoxamine and venlafaxine raise the levels of serotonin in the brain. Giving medications that work with the same mechanism in combination can lead to overstimulation of that pathway resulting in serious side effects. In the case of fluvoxamine and venlafaxine, this pathway involves ‘serotonin’. 

The potential and most common side effect of giving these drugs in combination is ‘serotonin syndrome’. It is a serious condition but is encountered rarely in which there is a positive agonism of serotonin in the central nervous system. The signs and symptoms are listed below.

Mental status changes:

• Confusion
• Hallucination
• Irritability
• Coma

Autonomic dysfunction:

• Increased heart rate/tachycardia
• Extreme changes in blood pressure
• Excessive sweating/diaphoresis
• Fever/hyperthermia
• Mydriasis

Neuromuscular abnormalities:

• Tremor
• Rigidity
• Ataxia
• Hyperreflexia
• Myoclonus

Gastrointestinal symptoms:

• Abdominal cramp
• Nausea
• Diarrhoea
• Vomiting

Severe cases of serotonin syndrome can also lead to coma and death.

How serotonin syndrome can be managed?

In case drugs from SSRI or SNRI classes are being administered, close monitoring is required. 

Mild symptoms: Withdraw the use of the offending agent, provide supportive care (adjustment of vital signs) and benzodiazepines can also be administered.

Moderate symptoms: Apart from the above-mentioned usage of 5-HT2A antagonists (cyproheptadine, chlorpromazine, atypical antipsychotics)

Severe symptoms: Apart from the above-mentioned, sedation, intubation, mechanical ventilation and neuromuscular paralysis. (2)

What research studies have been conducted to study the synergistic effect?

There is limited research available discussing the synergistic effect of fluvoxamine and venlafaxine. Sometimes antidepressants are used in combination depending on the clinical situation but the evidence of the usage and effect are not present in the scientific literature.

Research is available in which the efficacy and side effect profiles of fluvoxamine and venlafaxine are discussed. The focus of the research is to identify which drug is more tolerable, more acceptable for a specific condition and more efficacious.

More research needs to be done in this area to find out the dose that is acceptable for the concurrent administration of drugs. This can help potentiate the serotonergic effect without causing serotonin syndrome which can be life-threatening.

What are the recommendations for healthcare professionals and patients?

Fluvoxamine and venlafaxine combination can be considered in certain clinical cases, but careful evaluation is required by a healthcare professional. It is important to assess the potential benefits and risks for individual patients.

The assessment might be based on the severity of the individual case, response to treatment previously administered and need for therapy with a dual-action approach which targets different aspects of serotonin modulation.

It is very important for patients to openly discuss the signs and symptoms they experience after taking medications with their healthcare professionals. Apart from this, they should also state any supplements or over-the-counter medications that they are taking. This allows the healthcare professional to make better treatment plans and adjust the dosage or avoid any drug interactions.

It is very important to never self-prescribe or adjust the dose of the medications without consulting with a healthcare professional. They have more knowledge and experience to deal with your concerns and provide you with an individualized solution.

Conclusion

In my opinion, there is a possibility of the serotonin neurotransmitter being increased if fluvoxamine and venlafaxine are administered together. Therefore, close monitoring is required in case a clinical situation requires the concomitant use of both drugs. We have also discussed how the potential side effects can be managed in this article.

References