Trigestrel 0,05 mg/0,03 mg/0,075 mg/0,04 mg/0,125 mg Tablets

TRIGESTREL is indicated for fertility control in women and for the control of certain menstrual irregularities i.e. symptomatic treatment of primary dysmenorrhoea where contraception is also desired, and in cases of dysfunctional uterine bleeding.

Posology

FOR CONTRACEPTION

TRIGESTREL tablets must be taken as directed and at intervals not exceeding 24 hours to achieve maximum effectiveness. The tablets are to be taken at the same time every day, preferably after the evening meal or at bedtime. It can be expected to have withdrawal bleeding within 2 to 3 days after the last yellow tablet has been taken.

If the tablets have been started after day 5 or postpartum, the possibility of pregnancy must be checked prior to commencement of administration as conception or ovulation might have occurred before starting.

First Cycle

The patient is instructed to take the first TRIGESTREL tablet on the first day of the menstrual cycle (first day of bleeding). The first tablet should be selected from those in the red area of the pack marked with the appropriate day of the week. Thereafter, one tablet is taken daily, following the arrows marked on the package until all the tablets have been taken. Withdrawal bleeding should occur within 2 to 4 days after the patient has taken the last yellow tablet.

NOTE

If for some reason, the tablets are not started on day 1 of the cycle, an additional method of contraception (mechanical) should be used until 14 tablets of the first course of TRIGESTREL have been taken.

New patients with a history of short menstrual cycles (i.e. less than 25 days) should also use a supplementary, nonsteroidal method of contraception (e.g. mechanical) until they have taken a tablet daily for 14 consecutive days.

Subsequent Cycles

A new pack should be started the day after completion of the previous pack by taking the tablet in the red area of the new pack indicated with the appropriate day of the week. There must be no interruption of treatment, i.e. the new pack is started immediately after completion of the previous pack and each new pack is started with the same tablet in the red area of the pack even if withdrawal bleeding has not occurred or is still in progress. This method should continue for as long as contraception is desired. Each cycle or pack will begin on the same day of the week.

Patients changing from another oral contraceptive product

When changing from another oral contraceptive, begin the first active tablet of TRIGESTREL on the day after the last active tablet of the previous course has been taken. If a tablet-free interval is taken (if TRIGESTREL is started on the day when the new pack of the previous product was meant to start), then extra contraception methods (mechanical) are advised for the first 7 days. If the inert tablets are inadvertently taken first, extra contraceptive precautions are necessary during the first 14 days. If transient spotting or breakthrough bleeding occurs, continue with the course. If the bleeding is persistent or prolonged, consult a physician.

In the non-lactating mothers, use of TRIGESTREL tablets may be instituted immediately after delivery or at the first postpartum examination, whether or not menstruation has resumed.

Missed tablets

If a tablet is missed, the risk of pregnancy is greatest when it happens at the beginning or end of a cycle. The missed tablet should be taken as soon as possible. If tablets are missed for two consecutive days, both tablets should be taken as soon as possible. In either case, the next tablet should be taken at the usual time. Extra contraception methods (mechanical) are required for the next 7 days.

If three consecutive tablets are missed, TRIGESTREL should be discontinued, and remaining tablets discarded. A new package should be started on the eighth day after the last tablet was taken. Extra contraception methods (mechanical) are required for the 7 days while no tablets are taken and for 7 days after the new course has been started. If the patient does not have a period at the end of the second pack, she must return to her doctor to exclude the possibility of pregnancy.

Missing any of the inert tablets is not important, but the next course must be started at the right time.

Method of administration

Take TRIGESTREL tablets orally.

• Hypersensitivity to TRIGESTREL or to any components of the formulation.
• Suspected pregnancy.
• The presence, history or high risk of thromboembolic disease.
• Cerebrovascular disease.
• Previous myocardial infarction.
• Known or suspected coronary artery disease.
• Hyperlipidaemia.
• Known or suspected carcinoma of breast, endometrium or other hormone dependent/responsive neoplasias.
• Hepatic adenoma.
• Abnormal, undiagnosed genital bleeding.
• History or presence of liver tumours or impaired liver functions or cholestasis.
• Acute or chronic liver diseases, including Dubin-Johnson or Rotor syndromes.
• A history during pregnancy of pruritus or cholestatic jaundice.
• Presence of, or multiple risk factors for arterial disease.
• Severe or focal migraine.
• A history during pregnancy of chorea, herpes gestationis, pemphigoid gestationis or deteriorating otosclerosis.
• Depression not well controlled with treatment.
• A history of depression with the use of hormonal contraceptives.

Use TRIGESTREL with caution in patients with:

• Other forms of migraine headaches. TRIGESTREL should be stopped immediately if a migraine becomes focal. See section 4.3.
• Hypertension.
• Diabetes mellitus. u2013 Monitor carefully as a decrease in glucose tolerance may occur.
• Gallbladder disease.
• Depression. u2013 Discontinue TRIGESTREL if depression recurs.
• Porphyria.
• Conditions influenced by fluid retention, epilepsy and asthma, as the condition may be exacerbated.
• Varicose veins.

The risk of cardiovascular adverse effects such as thromboembolism is increased in women who smoke, especially those over the age of 35 years. The risk is greater if they have used oral contraceptives for longer than 5 years, if they are obese, hypertensive, diabetic or have hypercholesterolaemia. Women who take TRIGESTREL should be advised not to smoke.

Note: TRIGESTREL does not protect against sexually transmitted diseases or the virus that causes acquired immunodeficiency syndrome (AIDS).

TRIGESTREL should be discontinued immediately if any of the following occur:

• Sudden severe chest pain, sudden breathlessness, or severe pain / swelling in calf of one or both legs, as these may indicate thromboembolism or thrombotic disease.
• Unusual, severe prolonged headache, sudden disturbances of vision or hearing or other perceptual disorders, collapse, marked numbness or weakness affecting one side of the body or other signs or symptoms suggestive of cerebrovascular accident.
• Hepatitis, jaundice, generalised itching, liver enlargement, severe upper abdominal pain. Benign hepatic adenomas have been associated with the use of oral contraceptives, including TRIGESTREL.
• Onset of severe depression. Mood changes and depression are side effects reported with the use of hormonal contraceptives including TRIGESTREL. There is some evidence that hormonal contraceptive use may be associated with severe depression and a higher risk of suicidal thoughts/behaviour (e.g. talking about suicide, withdrawing from social contact, having mood swings, being preoccupied with death or violence, feeling hopeless about a situation, increasing use of alcohol/drugs, doing self-destructive things, personality changes) and suicide. Prescribers should inform their patients to contact their doctor for advice if they experience mood changes and depression whilst on treatment with TRIGESTREL.
• Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their medical practitioner in case of mood changes and depressive symptoms, including shortly after initiating the treatment.
• A significant rise in blood pressure.
• Clear exacerbation of other conditions known to be capable of deteriorating during oral contraception or pregnancy.

Women undergoing surgery or prolonged bed rest should discontinue TRIGESTREL four to six weeks before and for two weeks thereafter to minimize the possibility of thromboembolism after surgery.

Oral contraceptive failure may occur with concomitant antibiotic therapy. For maximal protection, additional non-hormonal contraception is recommended for the duration of antibiotic therapy and for seven days thereafter. Spotting and breakthrough bleeding are possible signs of diminished contraceptive effectiveness.

Oral contraceptive effectiveness may be reduced during vomiting and diarrhoea. Additional contraceptive measures may be necessary during and for 7 days after recovery from such episodes. Spotting and breakthrough bleeding are possible signs of diminished contraceptive effectiveness and additional contraceptive methods should be used. Changing to a product with a different composition may be required to ensure efficacy.

Excipients: Lactose and sucrose warning: TRIGESTREL contains lactose and sucrose which may have an effect on the glycaemic control of patients with diabetes mellitus.

Patients with the rare hereditary condition of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption, fructose intolerance or sucrose- isomaltase insufficiency should not take TRIGESTREL.

Enzyme-inducing medicines may enhance metabolism and clearance of oral contraceptives resulting in failure of the contraceptive effect. This effect is well established for a number of antiepileptics (such as carbamazepine, phenobarbital and phenytoin), griseofulvin, rifamycin antibacterials (such as rifampicin and rifabutin) and has also been suggested for some antivirals and for modafinil.

The following medicines may also interact with TRIGESTREL:

• Antibacterials: Broad-spectrum antibacterials have occasionally been reported to decrease oral contraceptive efficacy. See section 4.3.
• Antidiabetics: Troglitazone is an enzyme inducer and increases the clearance of estrogens and progestogens.
• Antiepileptics: Oral contraceptive failure and breakthrough bleeding have been reported in women on antiepileptic therapy. Phenytoin, phenobarbital, primidone and carbamazepine have been most frequently implicated, and oxcarbazepine, felbamate and topiramate may interact similarly. The effect of these may also be diminished due to the combined oral contraceptive.
• Antifungals: Menstrual irregularities and pregnancies have been reported in women receiving oral contraceptives including TRIGESTREL and griseofulvin concurrently. Reports have also been received of contraceptive failure with fluconazole, itraconazole and ketoconazole.
• Antivirals: Antivirals are likely to accelerate the metabolism of estrogen and progestogens and this has been suggested for the protease inhibitors such as nelfinavir and ritonavir, and for nevirapine.

Hypericum/St Johnu2019s Wort: May decrease blood concentrations of oral contraceptives resulting in intermenstrual and altered menstrual bleeding and contraceptive failure.

Stimulants: Modafinil may reduce the efficacy of oral contraceptives.

In addition to the above interactions, several medicines may be affected by concomitant use with TRIGESTREL:

• paracetamol and morphine u2013 analgesic effects antagonised
• anticoagulants u2013 increased or decreased effects
• antidepressants u2013 both reduced effectiveness and increased toxicity reported with some antidepressants
• antidiabetics such as sulfonylureas and insulin u2013 antagonism of the effect
• antihypertensives u2013 antagonism of the effect
• benzodiazepines u2013 increased or decreased clearance
• ciclosporin u2013 increased plasma concentration resulting in toxicity
• clofibrate u2013 increased clearance and antagonism of the effect
• corticosteroids u2013 enhanced effect due to reduced clearance
• lidocaine u2013 increased free fraction
• selegiline u2013 decreased clearance
• thyroxine u2013 reduced free fraction
• xanthines u2013 decreased clearance

Laboratory tests: TRIGESTREL may influence results such as liver, thyroid, adrenal and renal function tests, plasma concentrations of binding proteins and lipid/lipoprotein fractions, and fibrinolysis and coagulation parameters.

Pregnancy

Oral contraceptives are contraindicated in pregnancy. See section 4.3. Pregnancy should be ruled out before a course of TRIGESTREL is initiated. If two consecutive menstrual cycles have been missed, the use of TRIGESTREL should be discontinued until the possibility of pregnancy has been ruled out if the correct dosing schedule was followed. If not, pregnancy should be ruled out after the first missed menstrual period. It is recommended that conception be delayed for 3 months after discontinuation of TRIGESTREL or until after the first regular menses.

Breastfeeding

TRIGESTREL may diminish the quantity, quality or the length of time of lactation. TRIGESTREL is recommended to begin after the third postpartum month for mothers who are exclusively breastfeeding and in the third postpartum week for mothers who are only partially or not breastfeeding.

Based on the side effect profile of TRIGESTREL, no effect is expected on the ability to drive and use machines.

Tabulated summary of adverse reactions: The undesirable effects are listed by system organ classes.

System organ class Frequency Adverse reaction

Neoplasms benign [and], malignant and unspecified (including cysts and polyps) Less frequent: Breast tumours, hepatocellular carcinoma, benign hepatic tumours (adenomas) Frequency unknown: Increased risk of cervical cancer

Metabolism and nutrition disorders Frequent: Water retention Less frequent: Reduced glucose tolerance, changes in lipid metabolism, weight gain

Psychiatric disorders: Less frequent: depression and other mental changes

Nervous system disorders: Less frequent: worsening or increasing frequency of headache or migraines, chorea

Eye disorders: Frequency unknown: Intolerance to contact lenses has been reported and vision may deteriorate in myopic patients

Cardiac disorders: Less frequent: Hypertension

Vascular disorders: Less frequent: Venous thromboembolism, thrombosis, stroke

Gastrointestinal disorders: Frequent: Nausea and/or vomiting, bloating, abdominal cramps

Hepato-biliary disorders: Frequency unknown: Impaired liver function, gall bladder disease

Skin and subcutaneous tissue disorders: Less frequent: Chloasma (melasma), skin rashes, gain or loss of body or facial hair

Reproductive system and breast disorders: Frequent: Breast tenderness and menstrual irregularities such as spotting, breakthrough bleeding or amenorrhoea Less frequent: Changes in libido, vaginal candidiasis

Post marketing reported side effects: The following side effects have been reported with the post marketing use of hormonal contraceptives: Severe depression with a higher risk of suicidal thoughts/behaviour and suicide

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Symptoms of overdose

See section 4.8 Nausea may occur and withdrawal bleeding may occur in females.

Treatment of overdose

Treatment is symptomatic and supportive.