Dienosis Special Precautions

Before starting Dienogest 2 mg tablets treatment, pregnancy must be excluded (see Use in Pregnancy & Lactation). During treatment, patients are advised to use non-hormonal methods of contraception (e.g. barrier method) if contraception is required.
Pregnancies that occur among users of progestogen-only preparations used for contraception (eg. minipill) are more likely to be ectopic than are pregnancies among users of combined oral contraceptives. Therefore, in women with a history of extrauterine pregnancy or an impairment of tube function, the use of Dienogest 2 mg tablets should be decided on only after carefully weighing the benefits against the risks.
As Dienogest 2 mg tablets is a progestogen-only preparation, it can be assumed that special warnings and special precautions for use of other progestogen-only preparations are also valid for the use of Dienogest 2 mg tablets although not all of the warnings and precautions are based on respective findings in the clinical studies with Dienogest 2 mg tablets.
If any of the conditions/risk factors mentioned as follows is present or deteriorates, an individual risk-benefit analysis should be done before Dienogest 2 mg tablets is started or continued.
Circulatory disorders: The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products such as dienogest may have up to twice this level of risk. The decision to use any product other than one with the lowest VTE risk should be taken only after a discussion with the woman to ensure she understands the risk of VTE with dienogest, how her current risk factors influence this risk, and that her VTE risk is highest in the first ever year of use. There is also some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more.
In women who do not use a CHC and are not pregnant, about 2 out of 10,000 will develop a VTE over the period of one year. However, in any individual woman, the risk may be far higher, depending on her underlying risk factors.
Epidemiological studies in women who use low-dose (<50 μg ethinylestradiol) CHCs have found that out of 10,000 women, between 6 to 12 will develop a VTE in one year. It is estimated that out of 10,000 women who use a levonorgestrel-containing CHC, about 6 will develop a VTE in one year.
It is not yet known how the risk of VTE with CHCs that contain dienogest compares with the risk with levonorgestrel-containing CHCs.
Extremely rarely, thrombosis has been reported to occur in other blood vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries, in CHC users.
Tumors: A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR=1.24) of having breast cancer diagnosed in women who are currently using oral contraceptives (OCs), mainly estrogen-progestogen preparations. The excess risk gradually disappears during the course of the 10 years after cessation of combined oral contraceptives (COC) use. Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer. The risk of having breast cancer diagnosed in progestogen-only pill users is possibly of similar magnitude to that associated with COC. However, for progestogen-only preparations, the evidence is based on much smaller populations of users and so is less conclusive than that for COCs. These studies do not provide evidence for causation. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in OC users, the biological effects of OCs or a combination of both. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.
In rare cases, benign liver tumors, and even more rarely, malignant liver tumors have been reported in users of hormonal substances such as the one contained in Dienogest 2 mg tablets. In isolated cases, these tumors have led to life-threatening intra-abdominal hemorrhages. A hepatic tumor should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal hemorrhage occur in women taking Dienogest 2 mg tablets.
Changes in bleeding pattern: Dienogest 2 mg tablets treatment affects the menstrual bleeding pattern in the majority of women (see Adverse Reactions).
Uterine bleeding, for example in women with adenomyosis uteri or uterine leiomyomata, may be aggravated with the use of Dienogest 2 mg tablets. If bleeding is heavy and continuous over time, this may lead to anemia (severe in some cases). Discontinuation of Dienogest 2 mg tablets should be considered in such cases.
Changes in Bone Mineral Density (BMD): The use of Dienogest 2 mg tablets in adolescents (12 to 18 years) over a treatment period of 12 months was associated with a mean decrease in bone mineral density (BMD) in the lumbar spine of 1.2%. After cessation of treatment, BMD increased again in these patients.
Loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if BMD decrease in this population will reduce peak bone mass and increase the risk for fracture in later life (see Additional information on special populations: Paediatric population under Dosage & Administration and Pharmacology: Pharmacodynamics under Actions).
Therefore, the treating physician should weigh the benefits of Dienogest 2 mg tablets against the possible risks of use in each individual adolescent patient also taking into account the presence of significant risk factors for osteoporosis.
Adequate intake of calcium and Vitamin D, whether from the diet or from supplements, is important for bone health in women of all ages.
No BMD decrease was observed in adults (see Pharmacology: Pharmacodynamics under Actions).
Other conditions: Patients who have a history of depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.
Dienogest 2 mg tablets generally does not appear to affect blood pressure in normotensive women. However, if a sustained clinically significant hypertension develops during the use of Dienogest 2 mg tablets, it is advisable to withdraw Dienogest 2 mg tablets and treat the hypertension.
Recurrence of cholestatic jaundice and/or pruritus which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of Dienogest 2 mg tablets.
Dienogest 2 mg tablets may have a slight effect on peripheral insulin resistance and glucose tolerance. Diabetic women, especially those with a history of gestational diabetes mellitus, should be carefully observed while taking Dienogest 2 mg tablets.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking Dienogest 2 mg tablets.
Persistent ovarian follicles (often referred to as functional ovarian cysts) may occur during the use of Dienogest 2 mg tablets. Most of these follicles are asymptomatic, although some may be accompanied by pelvic pain.
Medical examination: A complete medical history should be taken and a physical and gynecological examination should be performed prior to the initiation or reinstitution of the use of Dienogest 2 mg tablets, guided by the contraindications (see Contraindications) and warnings (see Precautions), and these should be repeated regularly during the use of Dienogest 2 mg tablets. The frequency and nature of these assessments should be adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, and should also include cervical cytology.
Effects on ability to drive or use machines: Not known.