Isotretinoin and interactions with other medicines

Isotretinoin alone requires careful monitoring, and combining it with other drugs and supplements can both increase its toxicity and undermine the safety of the entire treatment regimen. Some combinations are expressly prohibited by the instructions, others require caution. The editors have systematized the most important isotretinoin interactions and explained why they occur.

Tetracyclines: prohibited combination

Antibiotics of the tetracycline series - doxycycline, minocycline, tetracycline - are widely used to treat acne. It would be logical to assume that they can be combined with isotretinoin for a faster effect. However, this combination is contraindicated by official instructions.

The reason is the risk of idiopathic intracranial hypertension, also called pseudotumor of the brain. Both retinoids and tetracyclines alone are capable of increasing cerebrospinal fluid pressure; together, the risk increases. The condition is manifested by a severe headache, nausea, vomiting, double vision and swelling of the optic disc. Without timely treatment, vision loss is possible.

In practice, this means that when switching from an antibiotic to isotretinoin, the doctor completes the course of tetracycline before starting the retinoid. The patient, in turn, should not independently add doxycycline "for acne" or for any other reason without consulting a dermatologist.

Other groups of antibiotics, such as macrolides or beta-lactams, do not have such an interaction. If an infection that requires treatment occurs during a course of isotretinoin, the doctor will choose an antibiotic with this limitation in mind.

Vitamin A and other retinoids

Isotretinoin is a derivative of vitamin A, so the simultaneous use of supplements with vitamin A (retinol, retinyl palmitate) leads to the summation of the retinoid load. The instructions for the drug directly warn against such a combination due to the risk of hypervitaminosis A.

The symptoms of hypervitaminosis A partially coincide with the side effects of isotretinoin: dryness and peeling of the skin, headache, bone pain, nausea, changes in liver parameters. In severe cases — liver damage and increased intracranial pressure. Therefore, additional vitamin A actually increases the most unpleasant reactions.

• Avoid multivitamins high in retinol; plant-based beta-carotene carries a much lower risk.
• Do not combine with other oral retinoids (acitretin, alitretinoin).
• Cod liver oil contains a lot of vitamin A - it should be discussed with a doctor.
• Local retinoids (tretinoin, adapalene) during the course are usually not used due to excessive skin irritation.

Many sports complexes and "boosters" contain vitamin A as part of multivitamin formulas. Before starting treatment, you should review the composition of all the supplements you take and show it to your doctor.

Regarding vitamin E and vitamin D, no significant interactions with isotretinoin have been described. However, the principle "the less excess, the easier to control" remains relevant during any course of systemic retinoids.

Contraception and St. John's wort

For women of reproductive age, the most important interaction concerns contraception. Effective prevention of pregnancy is a mandatory condition of treatment due to the high teratogenicity of isotretinoin. Therefore, anything that reduces the reliability of contraceptives is actually a dangerous interaction.

St. John's wort (Hypericum perforatum), popularly known as a "natural antidepressant", induces CYP3A4 liver enzymes and accelerates the breakdown of hormonal contraceptives. The instructions for isotretinoin separately mention cases of pregnancy in women who simultaneously took oral contraceptives and St. John's wort. Such a combination is unacceptable.

Also, mini-dose tablets containing only progestogen are considered with caution: the instructions state that they may not be a sufficiently reliable method during treatment with isotretinoin. Pregnancy prevention programs usually require the use of one highly effective method or two complementary methods.

To avoid mistakes, the patient should inform the dermatologist and gynecologist about all drugs and supplements, including herbal ones. Even "harmless" mood tea can cause an unplanned pregnancy with serious consequences.

Liver and lipids: methotrexate, alcohol, steroids

Methotrexate, which is used for psoriasis and rheumatoid arthritis, has its own hepatotoxicity. The combination with isotretinoin, which can also increase liver enzymes, increases the risk of liver damage. Such a combination is possible only in special clinical situations and under the careful supervision of a specialist.

Alcohol is a common "invisible" interaction. It loads the liver and increases the level of triglycerides, and isotretinoin itself can increase triglycerides. Together, this increases the risk of severe hypertriglyceridemia and, as a result, pancreatitis. The guidelines advise to minimize the consumption of alcohol during the course.

Interaction with anabolic-androgenic steroids is especially important for our audience. Oral 17-alpha-alkylated drugs are hepatotoxic and dramatically lower HDL (Pope et al., 2014). In combination with isotretinoin, the load on the liver and lipid metabolism is added, and the interpretation of analyzes is complicated.

In addition, androgens themselves stimulate the sebaceous glands, so the effectiveness of isotretinoin against the background of their use is less predictable. From the point of view of both the skin and the organs, the most rational step is to eliminate the cause, and not to try to "cover" it with another strong drug.

Other drugs, supplements and procedures

Systemic corticosteroids with long-term use affect bone tissue; isotretinoin has also been associated with bone changes with long-term use. Although the clinical significance of this interaction is limited, physicians take it into account, especially in adolescents and young adults with intense skeletal stress.

Photosensitizing drugs—some diuretics, fluoroquinolones, nonsteroidal anti-inflammatory drugs, and furocoumarins from bergamot or St. John's wort—can increase skin sensitivity to the sun. Against the background of isotretinoin, which itself increases photosensitivity, the risk of burns and pigmentation increases.

Keratolytics and aggressive skin products (scrubs, acid peels, alcohol lotions) during the course increase irritation and dryness. Ablative laser treatments, dermabrasion, and waxing are usually delayed for at least six months after treatment is completed.

Finally, donating blood during the course and during the month after it is prohibited: blood with isotretinoin can get into the pregnant recipient. This is not a pharmacological interaction, but an important part of the safety program.

Editorial conclusion

The most dangerous interactions of isotretinoin are with tetracyclines (intracranial hypertension) and with vitamin A supplements (hypervitaminosis).

For women, it is critical to avoid anything that reduces the reliability of contraception, primarily St. John's wort and liver enzyme inducers.

Methotrexate, alcohol, and anabolic steroids add to the burden on the liver and lipids; photosensitizers and aggressive procedures increase skin damage.

We also recommend: "Side effects and contraindications of Isotretinoin", "Why do athletes need Isotretinoin" and "Interaction of citrus bergamot with other drugs".

References

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6. European Medicines Agency. Updated measures for pregnancy prevention during retinoid use. EMA; 2018.