Minulet Special Precautions

Special Warnings: Cigarette smoking increases the risk of serious cardiovascular adverse reactions from COC use. This risk increases with age and with the extent of smoking (in epidemiology studies, smoking 15 or more cigarettes per day was associated with a significantly increased risk), and is quite marked in women over 35 years of age. Women who use COCs should be strongly advised not to smoke.
Venous and arterial thrombosis and thromboembolism: Use of COCs is associated with an increased risk of venous and arterial thrombotic and thromboembolic events.
Minimizing exposure to estrogens and progestins is in keeping with good principles of therapeutics. For any particular estrogen/progestin combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestin that is compatible with a low failure rate and the needs of the individual patient.
New acceptors of COCs should be started on preparations containing less than 50 μg of estrogen.
Venous thrombosis and thromboembolism: Use of COCs increases the risk of venous thrombotic and thromboembolic events. Reported events include deep venous thrombosis and pulmonary embolism. For information on retinal vascular thrombosis see Ocular lesions as follows.
The use of any COC carries an increased risk of venous thrombotic and thromboembolic events compared with no use. The excess risk is highest during the first year a woman ever uses a combined oral contraceptive. This increased risk is less than the risk of venous thrombotic and thromboembolic events associated with pregnancy which is estimated as 60 cases per 100,000 women-years. Venous thromboembolism is fatal in 1% to 2% of cases.
Epidemiological studies have shown that the incidence of venous thromboembolism in users of low-estrogen oral contraceptives (<50 mcg ethinyl estradiol) ranges from about 20 to 40 cases per 100,000 women-years; this risk estimate varies according to the progestin. This compares with 5 to 10 cases per 100,000 women-years for non-users.
Several epidemiological studies have demonstrated that women who use COCs that contain ethinyl estradiol (particularly 30 μg) and a progestin such as gestodene are at increased risk for venous thrombotic and thromboembolic events compared with women who use COCs that contain less than 50 μg of ethinyl estradiol and the progestin levonorgestrel. However, data from other studies have not shown this increased risk.
For COCs containing 30 μg of ethinyl estradiol combined with desogestrel or gestodene compared with those containing less than 50 μg of ethinyl estradiol and levonorgestrel, the overall relative risk of venous thrombotic and thromboembolic events has been estimated to range between 1.5 and 2.0. The incidence of venous thrombotic and thromboembolic events for levonorgestrel-containing COCs with less than 50 μg of ethinyl estradiol is approximately 20 cases per 100,000 woman-years of use. For MINULET, the incidence is approximately 30-40 cases per 100,000 women-years of use, i.e., additional 10-20 cases per 100,000 woman-years of use.
All this information should be taken into account when prescribing this COC. When counseling on the choice of contraceptive method(s) all of the previously mentioned information should be considered.
The risk of venous thrombotic and thromboembolic events is further increased in women with conditions predisposing for venous thrombosis and thromboembolism. Caution must be exercised when prescribing COCs for such women.
Examples of predisposing conditions for venous thrombosis and thromboembolism are: obesity; surgery or trauma with increased risk of thrombosis; recent delivery or second-trimester abortion; prolonged immobilization; increasing age.
Further risk factors, which represent contraindications for the use of COCs, are listed in Contraindications.
The relative risk of postoperative thromboembolic complications has been reported to be increased two- to four-fold with the use of COCs. The relative risk of venous thrombosis in women with predisposing conditions is twice that of women without such conditions. If feasible, COCs should be discontinued: for four weeks prior to and for two weeks after elective surgery with increased risk of thrombosis, and during prolonged immobilization.
Because the immediate post-partum period is associated with an increased risk of thromboembolism, COC use should begin no sooner than the 28^th postpartum day following either delivery in a nonlactating woman or second-trimester abortion.
Arterial thrombosis and thromboembolism: The use of COCs increases the risk of arterial thrombotic and thromboembolic events. Reported events include myocardial infarction and cerebrovascular events (ischemic and hemorrhagic stroke, transient ischemic attack). For information on retinal vascular thrombosis see Ocular lesions as follows.
The risk of arterial thrombotic and thromboembolic events is further increased in women with underlying risk factors.
Caution must be exercised when prescribing COCs for women with risk factors for arterial thrombotic and thromboembolic events.
Examples of risk factors for arterial thrombotic and thromboembolic events are: smoking; hypertension; hyperlipidemias; obesity; increasing age.
COC users with migraine (particularly migraine with aura) may be at increased risk of stroke (see Contraindications).
Further risk factors, that represent contraindications for the use of COCs are listed in Contraindications.
Ocular lesions: With use of COCs, there have been reports of retinal vascular thrombosis, which may lead to partial or complete loss of vision. If there are signs or symptoms such as visual changes, onset of proptosis or diplopia, papilledema, or retinal vascular lesions, the COC should be discontinued and the cause immediately evaluated.
Blood pressure: Increases in blood pressure have been reported in women taking COCs.
In women with hypertension or a history of hypertension or hypertension-related diseases (including certain renal diseases), another method of birth control may be preferable. If COCs are used in such cases, close monitoring is recommended; if a significant increase in blood pressure occurs, COCs should be discontinued.
Elevated blood pressure associated with COC use will generally return to baseline after stopping COCs, and there appears to be no difference in the occurrence of hypertension among ever-and-never-users.
COC use is contraindicated in women with uncontrolled hypertension (see Contraindications).
Carcinoma of the reproductive organs: Cervical cancer: The most important risk factor for cervical cancer is persistent human papillomavirus infection.
Some studies suggest that COC use may be associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. For example, the results of one meta-analysis of 24 epidemiological studies indicated that among current users of oral contraceptives, the relative risk of invasive cervical cancer increased with increasing duration of use. The relative risk for 5 or more years' use versus never-use was 1.90 (95% confidence interval 1.69-2.13). The relative risk declined after use ceased and by 10 or more years was not significantly different from that in never-users. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behaviour and other factors. In cases of undiagnosed abnormal genital bleeding, adequate diagnostic measures are indicated.
Breast cancer: Established risk factors for the development of breast cancer include increasing age, family history, obesity, nulliparity, and late age for first full-term pregnancy.
A meta-analysis from 54 epidemiological studies reported that there is slightly increased relative risk (1.24) of having breast cancer diagnosed in women who are using COCs compared to never-users. The increased risk gradually disappears during the course of the 10 years after cessation of COC use. These studies do not provide evidence for causation. The observed pattern of increased risk of breast cancer diagnosis may be due to earlier detection of breast cancer in COC users (due to more regular clinical monitoring), the biological effects of COCs, or a combination of both. 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 lifetime risk of breast cancer. Breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.
Hepatic neoplasia/liver disease/hepatitis C: In very rare cases hepatic adenomas, and in extremely rare cases, hepatocellular carcinoma may be associated with COC use. The risk appears to increase with duration of COC use. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.
Women with a history of COC-related cholestasis and women who develop cholestasis during pregnancy are more likely to develop cholestasis with COC use. Such patients who use COCs should be carefully monitored and, COC use should be discontinued if cholestasis recurs.
Hepatocellular injury has been reported with COC use. Early identification of drug-related hepatocellular injury can decrease the severity of hepatotoxicity when the drug is discontinued. If hepatocellular injury is diagnosed, patients should stop their COC, use a non-hormonal form of birth control and consult their doctor.
Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until liver function has returned to normal.
ALT elevations: During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs). Patients who are taking ethinylestradiol-containing medicinal products must switch to an alternative method of contraception (e.g. progestin only contraception or non-hormonal methods) prior to initiating ombitasvir/paritaprevir/ritonavir and dasabuvir therapy (see Contraindications and Interactions).
Migraine/headache: The onset or exacerbation of migraine or development of headache with a new pattern that is recurrent, persistent or severe requires discontinuation of COCs and evaluation of the cause.
Women with migraine (particularly migraine with aura) who take COCs may be at increased risk of stroke. See Contraindications.
Immune: Angioedema: Exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema.
Precautions: Medical examinations: Before COC use is initiated, a thorough individual history, family history, and physical examination, including a blood pressure determination, should be performed. An examination of the breasts, liver, extremities, and pelvic organs should also be conducted. A Papanicolaou (Pap) smear should be performed if the patient has been sexually active or if it is otherwise indicated.
Such medical examinations should be repeated at least annually during the use of COCs.
The first follow-up visit should occur 3 months after COCs are prescribed. At each annual visit, examination should include those procedures that were performed at the initial visit, as described previously.
Carbohydrate and lipid effects: Glucose intolerance has been reported in COC users. Women with impaired glucose tolerance or diabetes mellitus who use COCs should be carefully monitored. See Contraindications.
A small proportion of women will have adverse lipid changes while taking OCs. Nonhormonal birth control should be considered in women with uncontrolled dyslipidemias. Persistent hypertriglyceridemia may occur in a small proportion of COC users. Elevations of plasma triglycerides in COC users may lead to pancreatitis and other complications.
Estrogens increase serum high-density lipoproteins (HDL cholesterol), whereas a decline in serum HDL cholesterol has been reported with many progestational agents. Some progestins may elevate low-density lipoprotein (LDL) levels and may render the control of hyperlipidemias more difficult. The net effect of a COC depends on the balance achieved between doses of estrogen and progestin and the nature and absolute amount of progestins used in the contraceptive. The amount of both hormones should be considered in the choice of a COC.
Women who are being treated for hyperlipidemias should be followed closely if they elect to use COCs.
Genital bleeding: In some women withdrawal bleeding may not occur during the tablet free interval. If the COC has not been taken according to directions prior to the first missed withdrawal bleed, or if two consecutive withdrawal bleeds are missed, tablet-taking should be discontinued and a nonhormonal back-up method of birth control should be used until the possibility of pregnancy is excluded.
Breakthrough bleeding/spotting may occur in women taking COCs, especially during the first three months of use. The type and dose of progestin may be important. If this bleeding persists or recurs, nonhormonal causes should be considered and adequate diagnostic measures may be indicated to rule out pregnancy, infection, malignancy, or other conditions. If pathology has been excluded, continued use of the COC or a change to another formulation may solve the problem.
Some women may encounter post-pill amenorrhea (possibly with anovulation) or oligomenorrhea, especially when such a condition was preexistent.
Depression: Women with a history of depression who use COCs should be carefully observed and the drug discontinued if depression recurs to a serious degree. Patients becoming significantly depressed while taking COCs should stop the medication and use an alternative method of birth control in an attempt to determine whether the symptom is drug-related.
Other: Patients should be counseled that this product does not protect against HIV infection (AIDS) or other sexually transmitted diseases.
Diarrhea and/or vomiting may reduce hormone absorption resulting in decreased serum concentrations (see Advice in case of vomiting and/or diarrhea under Dosage & Administration and Interactions).
Effects on ability to drive and use machines: The impact of MINULET on the ability to drive and use machines has not been systematically evaluated. MINULET is not expected to influence the ability to drive or use machines. Cases of dizziness have been reported. Patients should exercise caution until they know that MINULET does not affect these abilities.
Use in Children: Safety and efficacy of COCs have been established in women of reproductive age. Use of these products before menarche is not indicated.
Use in the Elderly: COCs are not indicated for use in postmenopausal women.