DIANE-35 TABLET [SIN04784P]

Product Info

DIANE-35 TABLET

[SIN04784P]

4.1 Indications

For the treatment of androgen-dependent diseases in women, such as moderate to severe acne, and mild forms of hirsutism.

When used for the treatment of acne, Diane-35 should only be used after topical therapy or systemic antibiotic treatments have failed.
If the hirsutism has only recently appeared or has lately intensified to a considerable extent, the cause (androgen-producing tumour or an adrenal enzyme defect) must be clarified by differential diagnosis.
Diane-35 should not be prescribed for the purpose of contraception alone.

4.2 Dosage and Method of Administration

Method of Administration

Oral use.

Dosage Regimen

How to take Diane-35

Diane-35 is to be taken regularly in order to achieve the therapeutic efficacy and the required contraceptive protection. Previously used hormonal contraception should be discontinued. The dose regimen of Diane-35 is similar to the usual regimen of most of the combined oral contraceptives. Thus, the same administration rules must be considered. Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1% per year. The irregular intake of Diane-35 can lead to intermenstrual bleedings and could deteriorate the therapeutic and contraceptive reliability.

Tablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. One tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day tablet-free interval, during which time a withdrawal bleed usually occurs. This usually starts on day 2–3 after the last tablet and may not have finished before the next pack is started.

How to start Diane-35

• No preceding hormonal contraceptive use (in the past month)

  Tablet-taking has to start on day 1 of the woman’s natural cycle (i.e. the first day of her menstrual bleeding). Starting on days 2–5 is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking.

• Changing from a combined hormonal contraceptive (Combined oral contraceptive/ COC), vaginal ring or transdermal patch

  The woman should start with Diane-35 preferably on the day after the last hormone-containing tablet of her previous COC, but at the latest on the day following the usual tablet-free or hormone-free tablet interval of her COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Diane-35 preferably on the day of removal of the last ring or patch of a cycle pack, but at the latest when the next application would have been due.

• Changing from a progestogen-only-method (minipill, injection, implant) or from a progestogen-releasing intrauterine system (IUS)

  The woman may switch any day from the minipill (from an implant or the IUS on the day of its removal, from an injectable when the next injection would be due), but should in all of these cases be advised to additionally use a barrier method for the first 7 days of tablet-taking.

• Following first-trimester abortion

  The woman may start immediately. When doing so, she does not need additional contraceptive measures.

• Following delivery or second-trimester abortion
  For breastfeeding women see section, “Pregnancy and Lactation” – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

  Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of Diane-35 use or the woman has to wait for her first menstrual period.

Management of missed tablets

If the user is less than 12 hours late in taking any tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time.

If she is more than 12 hours late in taking any tablet, contraceptive protection may be reduced.

The management of missed tablets can be guided by the following two basic rules:

1. tablet-taking must never be discontinued for longer than 7 days

2. 7 days of uninterrupted tablet-taking are required to attain adequate suppression of the hypothalamic-pituitary-ovarian-axis.

Accordingly the following advice can be given in daily practice:

• Week 1
  The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. In addition, a barrier method such as a condom should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are missed and the closer they are to the regular tablet-free interval, the higher the risk of a pregnancy.

• Week 2
  The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the 7 days preceding the first missed tablet, there is no need to use extra contraceptive precautions. However, if this is not the case, or if she missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days.

• Week 3
  The risk of reduced reliability is imminent because of the forthcoming tablet-free interval. However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed tablet the woman has taken all tablets correctly. If this is not the case, the woman should be advised to follow the first of these two options and to use extra precautions for the next 7 days as well.

  1. The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. The next pack must be started as soon as the current pack is finished, i.e., no gap should be left between packs. The user is unlikely to have a withdrawal bleed until the end of the second pack, but she may experience spotting or breakthrough bleeding on tablet-taking days.

  2. The woman may also be advised to discontinue tablet-taking from the current pack. She should then have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next pack.
     If the woman missed tablets and subsequently has no withdrawal bleed in the first normal tablet-free interval, the possibility of a pregnancy should be considered.

Advice in case of gastro-intestinal disturbances

In case of severe gastro-intestinal disturbances, absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3–4 hours after tablet-taking, the advice concerning missed tablets, as given in section, “Management of missed tablets”, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra tablet(s) needed from another pack.

Length of use

The length of use depends on the severity of the symptoms of androgenization and their response to treatment. In general, treatment should be carried out over several months. Time to relieve of symptoms is at least three months. Acne and seborrhea usually respond sooner than hirsutism. The need to continue treatment should be evaluated periodically by the treating physician.

Should there be a recurrence of symptoms, weeks or months after discontinuation of tablet-taking, treatment with Diane-35 may be resumed. In case of a restart of Diane-35 (following a 4-week or greater pill free interval), the increased risk of VTE should be considered (see section, “Special warnings and precautions for use” – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Additional information on special populations

Pediatric patients
Diane-35 is only indicated after menarche.

Geriatric patients
Not applicable. Diane-35 is not indicated after menopause.

Patients with hepatic impairment
Diane-35 is contraindicated in women with severe hepatic diseases as long as liver function values have not returned to normal. See also section, “Contraindication”.

Patients with renal impairment
Diane-35 has not been specifically studied in renally impaired patients. Available data do not suggest a change in treatment in this patient population.

4.3 Contraindications

Preparations containing estrogen/progestogen combinations should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during their use, the product should be stopped immediately.

• Concomitant use with another hormonal contraceptive (see section ‘Indications’)

• Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident.

• Presence or a history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris).

• Presence or history of cerebrovascular accident

• History of migraine with focal neurological symptoms.

• The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see ‘Special Warnings and Precautions for Use’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) such as:

  • Diabetes mellitus with vascular symptoms

  • Severe hypertension

  • Severe dyslipoproteinaemia

• Hereditary or acquired predisposition for venous or arterial thrombosis, such as activated protein C (APC) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).

• Severe hepatic disease as long as liver function values have not returned to normal.

• Use of direct-acting antiviral (DAA) medicinal products containing ombitasvir, paritaprevir, or dasabuvir, and combinations of these (see ‘Interaction with other medicinal products and other forms of interaction’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Presence or history of liver tumours (benign or malignant).

• Known or suspected sex-steroid influenced malignancies (e.g. of the genital organs or the breasts).

• Undiagnosed vaginal bleeding.

• Known or suspected pregnancy.

• Lactation.

• Hypersensitivity to the active substances or to any of the excipients.

Diane-35 is not for use in men.

Jaundice or persistent itching during a previous pregnancy, Dubin Johnson syndrome. Rotor syndrome, sickle cell anaemia existing or treated cancer of the breast or the endometrium, disturbances or lipometabolism, a history of herpes of pregnancy, otosclerosis with deterioration during pregnancy.