Izotek®: composition and pharmaceutical form
Izotek® comes in soft capsules, each containing 10 mg or 20 mg of isotretinoin. The two strengths are not a matter of convenience but of substance: the daily dose of isotretinoin is calculated per kilogram of body weight and adjusted during the course, so being able to combine capsules of different strength is essential.
The capsules contain refined, hydrogenated and partially hydrogenated soya oil. Because of this the medicine is not prescribed to people allergic to soya or peanuts — here the excipients matter as much as the active substance.
How Izotek® works
Isotretinoin is a stereoisomer of all-trans retinoic acid, that is of tretinoin. Its exact mechanism is not fully understood, but the main point is established: improvement in severe acne is linked to suppression of sebaceous gland activity, and the shrinkage of the glands themselves is confirmed histologically.
In addition, isotretinoin has an anti-inflammatory effect on the skin. The combination of the two effects — a sharp fall in sebum production and suppression of inflammation — explains why the medicine works where standard treatment with antibacterial agents has already proved powerless.
Indications
Izotek® is used in severe forms of acne: nodular acne, conglobate (clustered) acne, and also in acne carrying the risk of permanent scarring.
An essential caveat: this refers to forms resistant to adequately conducted standard treatment with systemic antibacterial agents and topical products. Isotretinoin is not prescribed for mild and moderate acne that has not been treated the usual way first.
Method of use and dosage
Only a doctor experienced in the use of systemic retinoids for severe acne, aware of the associated risks and of the patient monitoring requirements, may prescribe isotretinoin. The capsules are taken with food, once or twice a day.
| Situation | Dose |
|---|---|
| Start of treatment | 0.5 mg per kg of body weight per day |
| Usual working range | 0.5–1 mg per kg of body weight per day |
| Cumulative dose per course | 120–150 mg per kg; exceeding it brings no extra benefit |
| Course duration | usually 16–24 weeks |
| Severe renal impairment | start at 10 mg per day, then increase to 1 mg/kg or to the maximum tolerated dose |
| Repeat course | no earlier than 8 weeks after the previous one ends |
The dose is chosen individually: both the response to treatment and some of the adverse reactions depend on the dose and differ from person to person. The length of remission is determined by the cumulative dose received rather than by the length of the course or the daily dose. In most patients acne clears completely after a single course, and improvement may continue for up to 8 weeks after it ends — which is why a decision on a repeat course is not taken before that point. If tolerance is poor, treatment continues at a lower dose: the course becomes longer and the risk of relapse rises, but the therapy is not abandoned.
Contraindications
Isotretinoin is contraindicated in pregnancy and breastfeeding, and in women of childbearing potential unless all requirements of the Pregnancy Prevention Programme are met. The remaining prohibitions relate to metabolism and to the state of the liver.
- hypersensitivity to isotretinoin or to any component of the medicine;
- pregnancy and breastfeeding;
- childbearing potential outside the conditions of the Pregnancy Prevention Programme;
- hepatic impairment;
- markedly raised blood lipid levels;
- hypervitaminosis A;
- concomitant intake of tetracyclines;
- allergy to peanuts or soya.
Special warnings and precautions
Isotretinoin is a teratogen. This is not one warning among many but the defining property of the medicine: taking it during pregnancy leads to severe malformations of the foetus. For that reason its use in women of childbearing potential is possible only with full compliance with the Pregnancy Prevention Programme.
Mental state
In patients taking isotretinoin, depression and worsening of its symptoms, anxiety, a tendency to aggression, mood swings and psychotic disorders have been described, and very rarely suicidal thoughts, attempts and completed suicides. Particular caution is needed in those who have had depression in the past. Mood should be monitored in everyone, and at the first signs of depression the patient is referred to a specialist. It is important to understand: stopping the medicine may not by itself relieve the symptoms, so assessment by a psychiatrist and a psychologist is often required.
Skin, eyes and laboratory monitoring
- at the start of treatment acne sometimes flares; this usually passes within 7–10 days and does not call for a dose change;
- intense sun and ultraviolet light should be avoided, and if necessary a product with a factor of at least SPF 15 should be used;
- aggressive chemical dermabrasion and laser resurfacing are forbidden during treatment and for 5–6 months afterwards, and waxing for at least 6 months: scarring and permanent changes in skin colour are possible;
- topical keratolytics and exfoliating products are not used alongside the medicine — the skin becomes excessively irritated;
- a moisturising cream or ointment and a lip balm are needed from the first day of the course: dryness of the skin and lips develops almost always;
- dry eyes, corneal opacity and poorer vision in the dark are usually reversible, but wearing contact lenses may become impossible; night vision sometimes deteriorates suddenly, which matters behind the wheel;
- liver enzyme activity is checked before treatment starts, after a month and then every 3 months; on a persistent, clinically significant rise the dose is reduced or treatment is stopped;
- fasting blood lipids are monitored on the same schedule; triglyceride levels above 800 mg/dl (9 mmol/l) occur in acute pancreatitis, which can be fatal, so with an uncontrolled rise in triglycerides or signs of pancreatitis the medicine is withdrawn.
Drug interactions
Preparations containing vitamin A must not be taken together with isotretinoin: isotretinoin is itself a derivative of it, and such a combination threatens hypervitaminosis A.
The second firm restriction is tetracyclines. Cases of benign intracranial hypertension have been described with their concomitant use, so this combination is ruled out. Its signs are headache, nausea and vomiting, visual disturbances and papilloedema; if they appear the medicine is withdrawn immediately.
Pregnancy and breastfeeding
Use during pregnancy is prohibited unconditionally. If pregnancy occurs during treatment or within a month of stopping it, the risk of very severe foetal malformations is high. Exposure to isotretinoin is associated with malformations of the central nervous system (hydrocephalus, cerebellar anomalies, microcephaly), facial deformities, cleft palate, external ear defects up to its absence, microphthalmia, defects of the heart and great vessels and anomalies of the thymus and parathyroid glands. Spontaneous miscarriages are also more frequent.
If pregnancy does occur, treatment is stopped immediately and the woman is referred to a doctor specialising in teratology for assessment and counselling. Breastfeeding is likewise excluded: isotretinoin is highly lipophilic and very likely passes into breast milk.
Adverse effects
Most often the medicine causes dryness of the mucous membranes and skin: dry and inflamed lips, dryness of the nasal mucosa with nosebleeds, dry eyes, conjunctivitis and skin peeling. Some reactions are dose-dependent and usually ease after the dose is lowered or stopped, though certain ones persist even after the course has finished.
- very common: anaemia, raised ESR, thrombocytopenia or thrombocytosis, increased aminotransferase activity, rising triglycerides and falling high-density lipoproteins;
- very common in the eyes and skin: blepharitis, conjunctivitis, eye irritation, dermatitis, itching, erythematous rash, increased skin fragility;
- common: headache, neutropenia, joint and muscle pain, back pain (especially in adolescents);
- rare: depression, anxiety, tendency to aggression, mood swings, allergic skin reactions, anaphylactic reactions, hair loss;
- very rare but dangerous: suicidal thoughts and attempts, psychotic disorders, seizures, benign intracranial hypertension;
- very rare in the digestive tract: colitis, ileitis, haemorrhagic diarrhoea and inflammatory bowel disease, pancreatitis, gastrointestinal bleeding, hepatitis;
- very rare in the skin: acne fulminans, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis;
- very rare, other: hearing loss, vasculitis, glomerulonephritis, reduced bone density, calcification of ligaments and tendons, premature closure of the growth plates, diabetes mellitus.
Severe bloody diarrhoea, signs of intracranial hypertension, a marked allergic reaction and symptoms of pancreatitis are grounds for stopping the medicine at once and seeing a doctor without waiting for the scheduled visit.
Overdose
Isotretinoin is a derivative of vitamin A and its acute toxicity is low. Accidental intake of an excessive dose produces symptoms of hypervitaminosis A: severe headache, nausea and vomiting, drowsiness, irritability and itching. The signs of accidental and deliberate overdose are the same.
These manifestations are expected to be reversible and to resolve without specific treatment. Even so, the overdose should be reported to the doctor, if only so that the rest of the course can be adjusted.
How to get a prescription for Izotek® online
Izotek® is a prescription-only medicine and can be prescribed only by a doctor familiar with systemic retinoids and with the rules for monitoring the patient. During the online consultation the doctor will go through your situation, assess contraindications and test results and decide whether the medicine is indicated for you.
If the indications are confirmed, the doctor will issue an electronic prescription with which the medicine can be collected at a pharmacy. Women of childbearing potential will have the requirements of the Pregnancy Prevention Programme explained separately — treatment is not started without them.
