Isotretinoin use: best practice

Acne vulgaris is defined as a chronic inflammatory skin condition^​1​. Prevalence among adolescents and young adults in the UK has steadily increased over the past three decades. Between 1990 and 2021, prevalence in individuals aged 10–24 years rose by around 7.4%. In 2021, an estimated 14.6% of this age group were affected, placing the UK among the top ten countries globally for acne prevalence^​2​. Acne predominantly affects adolescents and young adults but can persist into adulthood, impacting quality of life and self-esteem^​2,3​.
 
Management of acne in the UK follows a stepwise approach based on severity and response to treatment. Mild cases are typically managed with topical therapies such as benzoyl peroxide, topical antibiotics or retinoids. For moderate acne, combination therapy, often benzoyl peroxide with a topical retinoid or a topical antibiotic is recommended, and oral antibiotics may be introduced for more persistent cases. Hormonal treatments, such as combined oral contraceptives, can be considered for suitable patients^​4​. 
 
In severe or treatment-resistant acne, oral isotretinoin is the gold standard, offering long-term remission but requiring strict monitoring owing to its safety profile. In addition to its well-known teratogenic risk, isotretinoin has been a subject of public concern regarding its potential psychiatric adverse effects. These concerns had resulted in regulatory bodies, such as the Medicines and Healthcare products Regulatory Agency (MHRA), issuing warnings and implementing enhanced monitoring requirements. 
 
Pharmacists play a pivotal role in ensuring the safe and effective use of isotretinoin across both primary and secondary care. In community pharmacy, pharmacists are often the first point of contact for patients seeking advice on side effects, skincare adjustments and safe use of other over-the-counter (OTC) products. They also play a critical role in reinforcing the pregnancy prevention programme (PPP) and ensuring adherence to treatment plans. In hospital settings, pharmacists are integral to monitoring blood tests, managing drug interactions and supporting dermatology teams in dose adjustments. Through proactive counselling and vigilance, pharmacists can optimise patient outcomes and maintain compliance.

Retinoids in acne

Retinoids are an umbrella term for all compounds that are chemically related to vitamin A. Retinol is the alcohol form of vitamin A and is a specific member of that group. It is the natural form of vitamin A and found in many skincare products. It is one of the most commonly sold OTC retinoids^​5,6​.

Figure 1: Retinoids

PubChem / The Pharmaceutical Journal / J Lipid Res. 2013 Jul;54(7):1731–1743. doi: 10.1194/jlr.R037648

Retinoic acid is the biologically active form that directly affects the skin. Other retinoids are inactive and must be converted into retinoic acid through a series of enzymatic oxidation steps. This conversion pathway generally progresses from retinyl esters to retinol, then to retinaldehyde, and finally to retinoic acid. With each step closer to retinoic acid, both efficacy and the likelihood of irritation increase. Isomers of retinoic acid do not require conversion to exert its effects. One such isomer is tretinoin (the all-trans-retinoic acid isomer)^​7​. In the UK, tretinoin is used topically and is seen in formulations such as gels or creams^​8​. It acts locally on the skin, binding to retinoic acid receptors, which increases cell turnover and unclogs pores. Tretinoin is used for mild-to-moderate acne. 
 
Isotretinoin is a 13-cisoretinoic acid isomer and is available as an oral formulation. In contrast to antibiotics or topical agents that address one or two aspects of acne, isotretinoin targets all the important drivers known to cause acne: sebum suppression, normalising keratinisation, reducing Cutibacterium acnes (C. acnes) and providing an anti-inflammatory effect^​9–13​. Isotretinoin is a very potent, systemic retinoid with long-lasting effects. As such, it is reserved for severe acne and is a last-line treatment. Isotretinoin is therapeutically indicated for severe forms of acne that have not improved with standard treatments, such as oral antibiotics and creams. This includes acne with large, painful lumps (i.e. nodular acne) or clusters of interconnected spots (i.e. conglobate acne), especially when there’s a high risk of permanent scarring^​4,14​. Patients can be considered for isotretinoin initiation if they have moderate-to-severe acne and have not responded to prior treatments, have scarring or experience a high psychosocial impact^​1​.

Isotretinoin initiation

Initiating isotretinoin requires strict protocols and careful patient education. Patients will have an assessment of their mental health prior to starting treatment. Clinicians should screen for symptoms of depression, mood changes, self-harm and suicidal ideation. This assessment is essential because acne itself can affect mental wellbeing and — although rare — isotretinoin has been associated with neuropsychiatric side effects^​15​. These factors should be considered when weighing the benefits versus risks of treatment. Ongoing monitoring at follow-up appointments supports early detection and intervention should any mental health concerns arise. Baseline blood results are required, which include hepatic function and serum lipids. Patients should receive full information regarding the possible side-effects, as well the benefits of this treatment, allowing them to make an informed decision.

For further details, see the later section on psychiatric side effects.

As part of the updated MHRA guidance, the previous requirements for an independent second prescriber before initiating isotretinoin in patients aged under 18 years has now been removed. Healthcare professionals may initiate isotretinoin to this age group without obtaining agreement from a second prescriber; however, all other risk minimisation measures remain in place, and the revised acknowledgement of risk form reflects this change. Importantly, the form also highlights that patients retain the right to seek a second opinion if they choose. In addition, a new patient information video produced to explain the risks of isotretinoin in a clear and accessible format should now be signposted to all patients, who are advised to watch it prior to starting treatment^​16​.

The initial isotretinoin dose is 0.5mg/kg daily in one-to-two divided doses orally. It is increased to 1mg/kg daily based on tolerance and response and is continued until a total cumulative dose of 120–150 mg/kg is achieved. The duration of treatment usually lasts 16–24 weeks, depending on the daily dose and response. Alternatively, treatment can be stopped once there has been sufficient response with no new lesions for at least 4 weeks, even if the cumulative dose is slightly lower^​14,17​.

Isotretinoin is contraindicated in pregnancy and breastfeeding owing to the severe risk of birth defects (teratogenicity). It cannot be commenced in patients of child-bearing potential unless all of the conditions outlined in the PPP are met. All patients of child-bearing potential must complete the acknowledgement of risk form and be enrolled in the PPP.

Isotretinoin commonly affects serum lipids, with triglycerides and total cholesterol rising and HDL-cholesterol occasionally falling during treatment. These changes are often dose-related and are reversible with dose reduction or discontinuation. If hypertriglyceridemia cannot be controlled, treatment should be stopped. As isotretinoin is metabolised in the liver, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations can occur. This is why isotretinoin is contraindicated in hepatic insufficiency. Co-administration with tetracyclines is contraindicated owing to the risk of intracranial hypertension. There should be no overlap when transitioning from antibiotics to isotretinoin^​18​.

Allergies and dietary considerations

The capsules contain a highly refined soya oil as an ingredient. In the UK, medicines containing soya typically carry a warning advising people with peanut or soya allergies to avoid them, owing to the potential risk of an allergic reaction. The precaution includes peanuts, even though isotretinoin does not contain peanut protein, as peanuts and soya belong to related plant families. However, after reviewing the evidence, UK allergy specialists, on behalf of the British Association of Dermatologists (BAD), have confirmed that individuals with a peanut allergy — but no soya allergy — can safely take isotretinoin^​19​.

Each isotretinoin capsule contains a small amount of highly processed soya oil, meaning that people with mild-to-moderate soya allergy can usually take the medication safely. Even though those with severe soya allergy may tolerate treatment, prescribers should seek advice from an allergy specialist before commencing isotretinoin in these^​20​. 

The capsules of all available brands of isotretinoin contain gelatine^{​18,21,22​}. There are no gelatine-free alternatives and, as such, should be highlighted to patients factoring in if they are vegetarian or vegan. The gelatine ingredient may be derived bovine (i.e. beef) or porcine (i.e. pork). Therefore, prior to initiating, ascertaining the patient’s religion and dietary requirements is an important factor to consider (e.g. specific brands use beef derived gelatine and are halal certified).

Pregnancy prevention programme 

Prior to commencing isotretinoin, it is mandatory for women of childbearing potential to be enrolled onto the PPP. At initiation, the prescriber has the responsibility to assess and document the PPP status of the patient on the acknowledgement of risk form, see Table 1.

Table 1: The four ‘Pregnancy prevention programme’ status categories

Patients are assigned one category. The category type is dependent on the whether the patient is sexually active or abstinent and the type of contraception they are on, if any. The PPP status dictates the maximum duration of isotretinoin that can be prescribed^​23​. Those that are sexually active and are within child-bearing age are required to be on a form of contraception. For pharmacists, it is vital to ensure the quantity of isotretinoin being prescribed on prescription is in line with PPP status.
 
It is strongly advised that individuals to wait at least one month after their last administered dose of isotretinoin before trying to conceive, ensuring the active metabolite is sufficiently cleared, thereby reducing the risk of teratogenic exposure. In pregnancy, there is on average a 3–5% chance of having a birth defect^​24​, which is increased in up to 28% or more if isotretinoin is taken during pregnancy. Birth defects been associated with small or absent ears, along with hearing and vision impairments^​25​. Other reported anomalies include congenital defects, cleft palate or absence of the thymus gland to name a few^​26​. If pregnancy occurs while on isotretinoin, termination is highly advised, as well as discontinuing isotretinoin.

Monitoring during treatment

Baseline blood assessments are essential, which includes liver function tests (LFTs) and fasting lipids. Full blood count (FBC) should also be carried out at baseline for safety; however, they are not mandatory in follow-ups.

The results of a retrospective cohort study by Emteani et al., published in 2024, encompassing more than 79,000 patients on isotretinoin for acne, found that within the first three months of initiating isotretinoin, patients had raised ALT and were 17 times more likely to experience hypertriglyceridaemia than patients who were commenced on oral antibiotics. Although the study results showed that isotretinoin resulted with a greater risk of hypertriglyceridaemia and hypertransaminasaemia, the absolute incidence of severe abnormalities was low^{​27–29​}. In continually raised serum lipids and/or LFTs, dose reduction or discontinuation is advised. 

Lipid and LFTs elevations are usually reversible upon discontinuation and do not pose significant long-term cardiovascular risks^​30,31​. Monitoring is required but can be scheduled. In 2023, the Isotretinoin Implementation Advisory Expert Working Group (IIAEWG) published the independent ‘Report of the Commission on Human Medicines Isotretinoin Implementation Advisory Working Group’^​23​. The report stipulates that bloods, including fasting serum lipids and liver enzymes, should be undertaken during the initiation of treatment. This should then be repeated after one month and subsequently at three monthly intervals thereafter, unless more frequent monitoring is clinically indicated.

Contraindications and cautions

For a summary of the absolute contraindications for isotretinoin and their rationales, see Table 2.

Table 2: Absolute contraindications for isotretinoin

Table 3 outlines cautions for isotretinoin and how to manage them^{​8,20–23​}.

Table 3: Cautions for isotretinoin

Adverse effects and practical management

The most common side-effects of isotretinoin involve the mucocutaneous, musculoskeletal and ophthalmic systems^​32​. Isotretinoin significantly reduces the sebaceous gland activity and alters the lipid composition of the skin and mucosa. This leads to a loss of natural protective barrier, resulting in an increase of transepidermal water loss (TEWL) and decreased skin hydration. The most common side-effect experienced by patients owing to this is severe dry skin (i.e. xerosis) and chapped lips (i.e. cheilitis)^​28,33​. Redness of the skin (i.e. erythema) and dry eyes are also common side-effects associated with this.

Dry skin can be managed using moisturisers. Cream-based formulations are recommended for mild dryness, whereas thicker ointments are more beneficial for more severe dryness. Moisturisers containing fragrance or alcohol can irritate and weaken the skin barrier, exacerbating dryness and inflammation^​34​. Patients on isotretinoin, fragrance-free and alcohol-free formulations are strongly recommended for this reason. Additionally, comedogenic ingredients should be avoided as it can block pores, leading to open and closed comedones^​17​. Ceramides are lipids found naturally on the skin. In acne affected skin, reduced ceramide levels have been observed, which may play a role in comedone formation^​35​. Ceramide-rich moisturisers are also recommended for this reason.

A 2020 review involving 38 studies examined the effects of omega 3 intake and skin health. The results of the review found that oral omega-3 also reduced mucocutaneous side effects associated with isotretinoin, which included dry lips, nose and skin^​36​. There is also evidence to suggest omega-3 oils improve lipid metabolism^​37​.

For more information about side effects and their management, see Figure 2^{​16,17,23,38–45​} .

Figure 2: Side effects

Psychiatric side effects

Among the public, psychiatric side effects are the most widely recognised risks associated with isotretinoin. This is heightened with the increasing use of social media for health information^{​46–49​}. Given the widespread circulation of anecdotal reports and misinformation on social media, pharmacists have an important role in supporting patients to interpret health information critically^​50​. By actively combating misinformation, pharmacists can reduce unnecessary anxiety, improve adherence and ensure that decisions about isotretinoin are founded on accurate evidence rather than online narratives^​51,52​. This is particularly valuable for young people, who are among the highest users of social media for health information and may be disproportionately exposed to such sources^​53,54​.

There is an ongoing debate, as there is currently conflicting literature linking isotretinoin to depression^{​55–57​}. It is hypothesised that isotretinoin may influence mood by interacting with neurotransmitter systems, such as dopamine and serotonin, potentially altering their levels and affecting psychiatric disorders^​58,59​. The results of a 2023 meta-analysis of 25 studies, covering over 1.6 million users, found a one-year absolute risk of suicide, suicidal ideation and self-harm among users to be less than 0.5% each and depression was found to be in 3.83%; therefore, although still an incident that may occur, it is a relatively rare incidence. At a population level, there was no increased risk of suicide or psychiatric disorders among those taking isotretinoin^{​60–63​}. Isolated cases can still exist, therefore patients that do experience signs of severe psychiatric changes, such as suicidal thoughts, should discontinue the medication immediately and seek urgent attention.

Interactions

Tetracycline antibiotics are contraindicated with isotretinoin owing to the risk of benign intracranial hypertension^​22​. Doxycycline can be used for the treatment of acne prior to initiating on isotretinoin^​64​. As a result, it is vital to do a full drug history prior to commencing and ensuring to regularly ask about other medications the patient may be taking. Pharmacists play an important role in this process, by reviewing prescriptions and counselling patients to ensure there are no interacting medicines dispensed. 

Isotretinoin is a systemic oral retinoid that can increase skin sensitivity and irritation. Combining this with other prescription or OTC acne treatments requires careful consideration to avoid reduced efficacy or exacerbating adverse effects^​17​. For this reason, other topical retinoids — such as adapalene, Epiduo or skincare products that contain exfoliating acids — such as salicylic acid and benzoyl peroxide, should be discontinued to avoid the increases risk of irritation and additive effects^​65​.

As the skin becomes more sensitive and fragile during treatment, physical exfoliants (i.e. scrubs) should be avoided owing to the likelihood of increased irritation. Cosmetic procedures, such as waxing, chemical peels and laser treatments, should also be avoided during and for six months post treatment^​17​.

Common patient questions and counselling advice

Patients may ask pharmacy professionals with questions regarding their condition and treatment. Some common questions and appropriate advice can be seen in Table 4^​66​. 

Table 4: Common questions asked by patients

Conclusion

This article has summarised evidence-based best practice for the use of oral isotretinoin in acne vulgaris. Applying these principles enables pharmacists across primary and secondary care to optimise efficacy, while minimising harm and ensuring compliance.