Doxefazepam: Fact Sheet & Harm Reduction Guide

By Enrique Santos Last Updated: January 18, 2024
Last Updated: January 18, 2024

Doxefazepam, also known as Doxans, is a short-acting benzodiazepine. It has an elimination half-life of three to four hours and an estimated duration of effects of two to eight hours. 

When it comes to its potency, one study concluded that doxefazepam has higher than average potency, being roughly two to three times as potent as diazepam (Valium) [1].

Doxefazepam was patented in 1972 and entered medical use in 1984 to treat insomnia-related issues. However, doxefazepam was only available in Italy, and by 1995, for unclear reasons, it was no longer available for purchase.

Doxefazepam Specs

StatusWas once an approved medication but is no longer sold (only in Italy)
Common Dosage20 mg
PubChem ID38668



Other Names: Doxans

Metabolism: doxefazepam’s metabolic pathways are hepatic. In humans, the drug is eliminated in the urine mainly as a conjugate, and two oxidative metabolites have been identified. Unfortunately, no studies have been done to determine what CYP enzymes are involved in its clearance.

Duration of Effects: doxefazepam is a short-acting compound. Its duration of effects is between two and eight hours.

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How Does Doxefazepam Work?

Doxefazepam exerts its effects by interacting with the benzodiazepine receptors found throughout the brain and central nervous system (CNS). These GABA-mediated receptors are the target of most “traditional” benzodiazepine drugs on the market, including alprazolam (Xanax), chlordiazepoxide (Librium), and lorazepam (Ativan). 

But how does it work exactly?

When benzodiazepine molecules bind to GABA-A receptors, they exert an allosteric effect that increases the inhibitory function of GABA receptors. This effect is achieved by increasing the opening frequency of the chloride channel found in GABA receptors. This allows the passage of negatively charged chloride ions into the neurons, which leads to a hyperpolarized state.

In this new hyperpolarized state, the neuron is less likely to fire off the electrical signals that are used by the nervous system to communicate. Thus a generalized depressive effect takes place.

There are also secondary mechanisms through which benzodiazepines work their magic, but these are much less understood. In reality, there is still lots that researchers don’t understand about this ‘traditional’ pathway. For instance, GABA receptors are made up of different subunits, and differences in benzodiazepine binding affinities in relation to these subunits seem to have an outsized effect on their pharmacology. However, the nature of the GABA-A subunits is still largely a mystery.

In the case of doxefazepam, the nature of the GABA-mediated pathway means it possesses anxiolytic, anticonvulsant, sedative, and muscle-relaxant properties, but clinically it is predominantly used as a hypnotic.

Is Doxefazepam Safe? Risks & Side Effects

According to an old study from 1975 (during the height of benzodiazepine research), doxefazepam was found to be roughly half as toxic in laboratory animals as its precursor, flurazepam, and causes significantly less hangover effect [1]. This is an important trait for a hypnotic medication as residual sedation is one of the most common side effects caused by these medications, which can significantly impair cognitive and physical performance.

This study would suggest that doxefazepam has a relatively safe profile as a hypnotic. However, doxefazepam is still a benzodiazepine, and, as such, it possesses a baseline level of risk that is still significant and must always be taken into account. 

In general, benzodiazepines are safe compounds when used responsibly. But serious health events and physical dependence may still happen, and the probability goes up significantly when misuse is factored into the equation.

Side Effects of Doxefazepam

Side effects and toxicology studies on doxefazepam suggest it is a well-tolerated benzodiazepine. One study, performed on mice, rats, and dogs, found that doxefazepam did not induce any pathological findings in the test subjects. In said study, doxefazepam did not exert any teratogenic effects, did not alter reproductive performance, and did not reveal any mutagenic potential [2]. 

The one adverse effect that appeared was dose-dependent, transient ataxia after administering doxefazepam. This side effect was only seen at the higher dosing ranges, though.

Unfortunately, there are no human studies that we can turn to regard doxefazepam’s side effects profile. However, doxefazepam is a metabolite of the benzodiazepine flurazepam, which is also an approved hypnotic medication. Since doxefazepam is a byproduct of flurazepam and both compounds are indicated for sleep-related disorders, we can likely assume they share similar adverse effects.

The FDA has identified the following side effects for flurazepam (Dalmane):

  • Ataxia
  • Coma (probably indicative of drug intolerance or overdosage)
  • Disorientation
  • Dizziness
  • Drowsiness
  • Falling (particularly in elderly or debilitated persons) 
  • Lethargy
  • Light-headedness
  • Severe sedation
  • Staggering

Other potential side effects include:

  • Apprehension
  • Body and joint pains
  • Chest pains
  • Constipation
  • Diarrhea
  • Gastrointestinal pain
  • Genitourinary complaints 
  • Headache
  • Heartburn
  • Irritability
  • Nausea
  • Nervousness
  • Palpitations
  • Talkativeness
  • Upset stomach
  • Vomiting
  • Weakness

Benzodiazepine Withdrawal & Dependence

In a benzodiazepine-related treatment, physical dependence and withdrawal symptoms are probably the number one issue that patients need to be aware of. In fact, it is only relatively recently that the medical community became aware of these issues and began to adjust benzodiazepine prescriptions accordingly. Unfortunately, the previous perception, wherein physical dependence is exceedingly rare and mainly comes about as a result of misuse, is still prevalent amongst the general public.

Doctors now exercise more care to hedge against the risk of physical dependence, mainly by limiting, as much as possible, the duration of treatment and the utilized dosage.

It is also important to understand that although all benzodiazepines carry this risk, some do so more than others. 

Research suggests four primary factors increase the risk of benzodiazepine dependence:

  1. Daily benzodiazepine use for a period of more than four months
  2. High dose (the higher the dose, the higher the dependence liability)
  3. Sudden cessation of benzodiazepine use
  4. Use of a short-acting benzodiazepine over a longer or intermediate-acting one

There is also other research to suggest that potency is a relevant factor. Several high-potency benzodiazepines are not recommended to be used for more than seven to 10 days due to their high dependence liability. In the case of doxefazepam, the compound is only meant to be used as a short-term treatment.

Harm Reduction: Doxefazepam

By following some simple harm reduction strategies, benzodiazepine users, whether prescription or recreational, can do much to mitigate risk.

For prescription users, the best strategy will always be to avoid misuse. In practical terms, this means following your prescription instructions extremely carefully. Even slight variations in dosage and formulation can make a difference. And in the case of a benzodiazepine hypnotic like doxefazepam, the time at which you’re supposed to take your medication is quite important: all hypnotic medications are supposed to be taken before going to bed.

As explained before, limiting the duration of treatment and the dosage is also effective in mitigating the possibility of physical dependence.

For recreational users, it doesn’t make much sense to recommend the avoidance of misuse. In their case, it’s more about advocating for different behavioral adjustments that can make a difference in avoiding serious health events like overdoses.

Recreational users should try their hardest to avoid mixing potent pharmacological compounds. And if they do so, they should at least try to mitigate this by considerably reducing the dosage. It is also a good idea to split up their intended dose into two halves or even four quarters. Doing drugs in a piecemeal fashion is an excellent strategy to avoid overdosing. Finally, it’s always best to have other people present as being alone means there won’t be anybody to help in case of an emergency.

Doxefazepam Drug Interactions 

Unless it’s with a doctor’s approval, benzodiazepine users should never mix compounds that can depress the central nervous system. 


Mixing two compounds of this nature potentiates the generalized depressive effect and will often put the user at risk of severe respiratory depression, the leading cause of death among drug overdoses. 

When using benzodiazepines, it is extremely important to avoid such compounds as opioids, alcohol, phenibut, and GHB. Anti-depressants, barbiturates, and other benzos. 

Doxefazepam Contraindications

Did you know that all benzodiazepines share a common set of contraindications? This is because of the shared nature of their principal mechanism of action.

Contraindications for benzodiazepines include:

  • Bronchitis
  • Chronic obstructive pulmonary disease (COPD)
  • Conjunctive use of barbiturates, opiates, or those suffering from alcoholism
  • Intellectual disabilities due to frequent paradoxical reactions
  • Major depression
  • Myasthenia gravis
  • Over the age of 65 (high risk)
  • Personality disorders 
  • Sleep apnea

Doxefazepam Dosage

Information on the proper dosage of doxefazepam is not easy to find. However, when it was available, it was sold in doses of 20 mg.

Similar Benzodiazepine Alternatives

The most similar compound to doxefazepam is flurazepam. Oxazepam is also considered to have very similar effects. 

The most common benzodiazepines on the market today include drugs like alprazolam (Xanax), chloridazepoxide (Librium), clonazolam (Klonopin), lorazepam (Ativan), etizolam, triazolam (Halcion), bretazenil, and bromazepam

All of these medications share similar effect profiles overall but feature unique characteristics. Some are more sedative, others more euphoric. The dosages and durations of action for these drugs can also vary substantially. 

Let’s cover the two most closely-related drugs to doxefazepam: 


Doxefazepam is one of the active metabolites of flurazepam. The general assumption is that byproducts usually hold at least some pharmacological resemblance to their parent compounds. 

This likely holds in this case, as both compounds are indicated as hypnotics. However, there are significant differences in terms of pharmacokinetics. Flurazepam is a long-acting compound that stays in the body for several days, while doxefazepam only has a duration of effects of two to eight hours. This is a big difference and is even more significant when the benzodiazepine is indicated as a hypnotic.



Oxazepam is one of the classic benzodiazepines when it comes to treating sleep-related disorders. Research suggests it exerts a similar pharmacological profile to doxefazepam. 

Additionally, it’s an intermediate-acting benzodiazepine, which is ideal for a hypnotic as the effects last through the night, but they don’t have as much chance to cause a hangover effect.


Doxefazepam FAQs

What is the effect of doxazepam on sleep?

Doxefazepam reduces the number of intermediate awakenings and the shifts between distinct sleep phases. Additionally, it significantly increases the total sleep duration and the percent duration of phase 2 and the synchronized sleep and decreases the percent duration of phase 1 and of the intermediate awakenings. Furthermore, volunteers report an improvement in the subjective ‘quality’ of sleep, while “hangover” effects were not reported [3]. All in all, research suggests doxefazepam is an effective sleep regulator.

It is worth noting, however, that these types of sleep studies are forced to rely on subjective, self-administered reports that attempt to define somewhat illusory qualities, like a dream “quality.”

Doxefazepam also has an effect on traditional patterns of electroencephalography (EEG) waves. The alteration of background EEG signals was detected after doxefazepam administration. These effects on EEG occurred relative to the administered dose and were congruent with the EEG profile known to be related to benzodiazepine compounds. 

However, the corresponding drug plasma concentrations of doxefazepam were remarkably lower than the minimum blood levels at which other benzodiazepines are reported to affect EEG waves. This suggests that doxefazepam has a particular affinity for GABA-A subunits that mediate for hypnotic properties. It is also important to note that, on the part of the patients, EEG alternations were not concomitant with subjective impairments [3].

What formulations is doxefazepam available in?

Doxefazepam was available in 20-mg capsules containing magnesium stéarate, mannitol, microgranular cellulose, precipitated silica, starch, and colorants.

Have any of the metabolites of doxefazepam been identified?

Yes. Some metabolites, such as glucuronide and the N-1-dealkylated and N-1-yl-acetic products, have been identified. However, the full extent of doxefazepam’s metabolic pathways and its byproducts has not yet been established [4].

Is doxefazepam well absorbed?

There isn’t much data available for doxefazepam’s pharmacokinetic values, but one study did conclude that the compound is rapidly absorbed and accumulates in adipose tissue after a relatively high oral dose (5 mg/kg) administered to rats [5].


  1. Babbini, M., Torrielli, M. V., Strumia, E., Gaiardi, M., Bartoletti, M., & De Marchi, F. (1975). Sedative-hypnotic properties of a new benzodiazepine in comparison with flurazepam. Pharmacological and clinical findings. Arzneimittel-forschung, 25(8), 1294-1300.
  2. Bertoli, D., Borelli, G., & Carazzone, M. (1989). Toxicological evaluations of the benzodiazepine doxefazepam. Arzneimittel-forschung, 39(4), 480-484.
  3. Rodriguez, G., Rosadini, G., Sannita, W. G., & Strumia, E. (1984). Effects of Doxefazepam on Normal Sleep. Neuropsychobiology, 11(2), 133-139.
  4. Mardente, S., Bicchi, C., & Nano, G. M. (1981). GLC-ECD determination of 1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1, 3-dihydro-5-(O-fluorophenyl)-2H-1, 4-benzodiazepin-2-one (SAS 643) in plasma and urine and identification of its main biotransformation products. Therapeutic Drug Monitoring, 3(4), 351-356.
  5. Marcucci, F., Garbagna, L., Monti, F., Bonazzi, P., Canobbio, L., Zuccato, E., & Mussini, E. (1980). Gas chromatographic determination of two fluorinated benzodiazepines in rats and mice. In Journal of Chromatography (pp. 180-184).