Dermavax Special Precautions

Teratogenic effects: DERMAVAX is a powerful human teratogen inducing a high frequency of severe and life threatening birth defects.
DERMAVAX is strictly contraindicated in: Pregnant women; Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met.
Pregnancy Prevention Programme: This medicinal product is TERATOGENIC.
Isotretinoin is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Programme are met: She has severe acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic anti-bacterials and topical therapy (see Indications/Uses).
The potential for pregnancy must be assessed for all female patients.
She understands the teratogenic risk.
She understands the need for rigorous follow-up on a monthly basis.
She understands and accepts the need for effective contraception, without interruption, 1 month before starting treatment, throughout the entire duration of treatment and for 1 month after the end of treatment. At least one highly effective method of contraception (i.e. a user-independent form) or two complementary user-dependent forms of contraception should be used.
Individual circumstances should be evaluated in each case, when choosing the contraception method, involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures.
Even if she has amenorrhea she must follow all of the advice on effective contraception.
She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy or if she might be pregnant.
She understands the need and accepts to undergo regular pregnancy testing before, ideally monthly during treatment and 1 month after stopping treatment.
She has acknowledged that she has understood the hazards and necessary precautions associated with the use of isotretinoin.
These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.
The prescriber must ensure that: The patient complies with the conditions for pregnancy prevention as listed previously, including confirmation that she has an adequate level of understanding.
The patient has acknowledged the aforementioned conditions.
The patient understands that she must consistently and correctly use one highly effective method of contraception (i.e. a user-independent form) or two complementary user-dependent forms of contraception, for at least 1 month prior to starting treatment and is continuing to use effective contraception throughout the treatment period and for at least 1 month after cessation of treatment.
Negative pregnancy test results have been obtained before, during and 1 month after the end of treatment. The dates and results of pregnancy tests should be documented.
If pregnancy occurs in a woman treated with isotretinoin, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice.
If pregnancy occurs after stopping treatment there remains a risk of severe and serious malformation of the foetus. This risk persists until the product has been completely eliminated, which is within one month following the end of treatment.
Contraception: Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception. If the prescribing physician is not in a position to provide such information the patient should be referred to the relevant healthcare professional.
As a minimum requirement, female patients of childbearing potential must use at least one highly effective method of contraception (i.e. a user-independent form), or two complementary user-dependent forms of contraception.
Contraception should be used for at least 1 month prior to starting treatment, throughout treatment and continue for at least 1 month after stopping treatment with isotretinoin, even in patients with amenorrhea.
Individual circumstances should be evaluated in each case, when choosing the contraception method involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures.
Pregnancy testing: According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL are recommended to be performed, as follows.
Prior to starting therapy: At least one month after the patient has started using contraception, and shortly (preferably a few days) prior to the first prescription, the patient should undergo a medically supervised pregnancy test. This test should ensure the patient is not pregnant when she starts treatment with isotretinoin.
Follow-up visits: Follow-up visits should be arranged at regular intervals, ideally monthly. The need for repeated medically supervised pregnancy tests every month should be determined according to local practice including consideration of the patient's sexual activity, recent menstrual history (abnormal menses, missed periods or amenorrhea) and method of contraception. Where indicated, follow-up pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber.
End of treatment: One month after stopping treatment, women should undergo a final pregnancy test.
Prescribing and dispensing restrictions: For women of childbearing potential, the prescription duration of DERMAVAX should ideally be limited to 30 days in order to support regular follow up, including pregnancy testing and monitoring. Ideally, pregnancy testing, issuing a prescription and dispensing of DERMAVAX should occur on the same day. Dispensing of isotretinoin should occur within a maximum of 7 days of the prescription.
This monthly follow-up will allow ensuring that regular pregnancy testing and monitoring is performed and that the patient is not pregnant before receiving the next cycle of medication.
Male patients: The available data suggest that the level of maternal exposure from the semen of the patients receiving DERMAVAX, is not of a sufficient magnitude to be associated with the teratogenic effects of DERMAVAX. Male patients should be reminded that they must not share their medication with anyone, particularly not females.
Additional precautions: Patients should be instructed never to give this medicinal product to another person, and to return any unused capsules to their pharmacist at the end of treatment.
Patients should not donate blood during therapy and for 1 month following discontinuation of isotretinoin because of the potential risk to the foetus of a pregnant transfusion recipient.
Educational material: In order to assist prescribers, pharmacists and patients in avoiding foetal exposure to isotretinoin the Marketing Authorisation Holder will provide educational material to reinforce the warnings about the teratogenicity of isotretinoin, to provide advice on contraception before therapy is started and to provide guidance on the need for pregnancy testing.
Full patient information about the teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme should be given by the physician to all patients, both male and female.
Psychiatric disorders: Depression, depression aggravated, anxiety, aggressive tendencies, mood alterations, psychotic symptoms, and very rarely, suicidal ideation, suicide attempts and suicide have been reported in patients treated with isotretinoin (see Adverse Reactions). Particular care needs to be taken in patients with a history of depression and all patients should be monitored for signs of depression and referred for appropriate treatment if necessary. However, discontinuation of isotretinoin may be insufficient to alleviate symptoms and therefore further psychiatric or psychological evaluation may be necessary.
Awareness by family or friends may be useful to detect mental health deterioration.
Skin and subcutaneous tissues disorders: Acute exacerbation of acne is occasionally seen during the initial period but this subsides with continued treatment, usually within 7-10 days, and usually does not require dose adjustment.
Exposure to intense sunlight or to UV rays should be avoided. Where necessary a sun-protection product with a high protection factor of at least SPF 15 should be used.
Aggressive chemical dermabrasion and cutaneous laser treatment should be avoided in patients on isotretinoin for a period of 5-6 months after the end of the treatment because of the risk of hypertrophic scarring in atypical areas and more rarely post inflammatory hyper or hypopigmentation in treated areas. Wax depilation should be avoided in patients on isotretinoin for at least a period of 6 months after treatment because of the risk of epidermal stripping.
Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase (see Interactions).
Patients should be advised to use a skin moisturising ointment or cream and a lip balm from the start of treatment as isotretinoin is likely to cause dryness of the skin and lips.
There have been post-marketing reports of severe skin reactions (e.g. erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) associated with isotretinoin use. As these events may be difficult to distinguish from other skin reactions that may occur (see Adverse Reactions), patients should be advised of the signs and symptoms and monitored closely for severe skin reactions. If a severe skin reaction is suspected, isotretinoin treatment should be discontinued.
Allergic reactions: Anaphylactic reactions have been rarely reported, in some cases after previous topical exposure to retinoids. Allergic cutaneous reactions are reported infrequently. Serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement have been reported. Severe allergic reactions necessitate interruption of therapy and careful monitoring.
Eye disorders: Dry eyes, corneal opacities, decreased night vision and keratitis usually resolve after discontinuation of therapy. Cases of dry eyes not resolving after discontinuation of therapy have been reported. Dry eyes can be helped by the application of a lubricating eye ointment or by the application of tear replacement therapy. Intolerance to contact lenses may occur which may necessitate the patient to wear glasses during treatment.
Decreased night vision has also been reported and the onset in some patients was sudden (see Effects on ability to drive and use machines as follows). Patients experiencing visual difficulties should be referred for an expert ophthalmological opinion. Withdrawal of isotretinoin may be necessary.
Musculo-skeletal and connective tissue disorders: Myalgia, arthralgia and increased serum creatine phosphokinase values have been reported in patients receiving isotretinoin, particularly in those undertaking vigorous physical activity (see Adverse Reactions). In some cases, this may progress to potentially life threatening rhabdomyolysis.
Bone changes including premature epiphyseal closure, hyperostosis, and calcification of tendons and ligaments have occurred after several years of administration at very high doses for treating disorders of keratinisation. The dose levels, duration of treatment and total cumulative dose in these patients generally far exceeded those recommended for the treatment of acne.
Sacroiliitis has been reported in patients exposed to isotretinoin. To differentiate sacroiliitis from other causes of back pain, in patients with clinical signs of sacroiliitis, further evaluation may be needed including imaging modalities such as MRI. In cases reported post-marketing, sacroiliitis improved after discontinuation of DERMAVAX and appropriate treatment.
Benign intracranial hypertension: Cases of benign intracranial hypertension have been reported, some of which involved concomitant use of tetracyclines (see Contraindications and Interactions). Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances and papilloedema. Patients who develop benign intracranial hypertension should discontinue isotretinoin immediately.
Hepatobiliary disorders: Liver enzymes should be checked before treatment, 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated. Transient and reversible increases in liver transaminases have been reported. In many cases these changes have been within the normal range and values have returned to baseline levels during treatment. However, in the event of persistent clinically relevant elevation of transaminase levels, reduction of the dose or discontinuation of treatment should be considered.
Renal insufficiency: Renal insufficiency and renal failure do not affect the pharmacokinetics of isotretinoin. Therefore, isotretinoin can be given to patients with renal insufficiency. However, it is recommended that patients are started on a low dose and titrated up to the maximum tolerated dose (see Dosage & Administration).
Lipid Metabolism: Serum lipids (fasting values) should be checked before treatment, 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated. Elevated serum lipid values usually return to normal on reduction of the dose or discontinuation of treatment and may also respond to dietary measures.
Isotretinoin has been associated with an increase in plasma triglyceride levels. Isotretinoin should be discontinued if hypertriglyceridaemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur (see Adverse Reactions). Levels in excess of 800 mg/dL or 9 mmol/L are sometimes associated with acute pancreatitis, which may be fatal.
Gastrointestinal disorders: Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. Patients experiencing severe (haemorrhagic) diarrhoea should discontinue isotretinoin immediately.
High Risk Patients: In patients with diabetes, obesity, alcoholism or a lipid metabolism disorder undergoing treatment with isotretinoin, more frequent checks of serum values for lipids and/or blood glucose may be necessary. Elevated fasting blood sugars have been reported, and new cases of diabetes have been diagnosed during isotretinoin therapy.
Effects on ability to drive and use machines: DERMAVAX could potentially have an influence on the ability to drive and use machines.
A number of cases of decreased night vision have occurred during isotretinoin therapy and in rare instances have persisted after therapy (see Precautions and Adverse Reactions). Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating machines.
Drowsiness, dizziness and visual disturbances have been reported very rarely. Patients should be warned that if they experience these effects, they should not drive, operate machinery or take part in any other activities where the symptoms could put either themselves or others at risk.