Consumer medicine information

Postella-1 Tablet

Levonorgestrel

BRAND INFORMATION

Brand name

Postella-1

Active ingredient

Levonorgestrel

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Postella-1 Tablet.

What is in this leaflet

Read this leaflet carefully before taking your medicine. This leaflet answers some common questions about this medicine. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

You can also download the most up to date leaflet from www.apotex.com.au.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

Keep this leaflet with your medicine. You may want to read it again.

What this medicine is used for

The name of your medicine is Postella-1 tablet. It contains the active ingredient levonorgestrel.

This medicine is an emergency contraceptive only. It is not intended as a regular method of contraception.

It is used to prevent pregnancy when taken within 72 hours of unprotected intercourse.

It is estimated that this medicine will prevent 85% of expected pregnancies.

The sooner that you take this medicine after unprotected intercourse, the more likely it is that it will work. This medicine is most effective if taken within 72 hours of unprotected intercourse. But remember, the sooner you take it, the more likely it will prevent pregnancy.

This medicine does not prevent you from catching sexually transmitted diseases such as HIV infection (AIDS), chlamydia, genital herpes, genital warts, gonorrhoea, hepatitis B, human papilloma virus and syphilis.

Ask your doctor or pharmacist if you have any questions about why this medicine has been recommended for you.

Use in children

This medicine is not recommended for children. There is only limited information available on this medicine when taken by females aged 14-16 years and no information on its use in younger females.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You are hypersensitive to, or have had an allergic reaction to, levonorgestrel or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include: cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin; fainting; or hay fever-like symptoms.
    If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
  • You are pregnant.
  • You have previously had unprotected intercourse more than 72 hours earlier in the same menstrual cycle, as you may already be pregnant.
  • You are experiencing unexplained vaginal bleeding.
  • You have breast cancer.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.

Before you start to take it

Before you start taking this medicine, tell your doctor or pharmacist if:

  1. You have allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • very high blood pressure
  • diabetes mellitus (with kidney, eye or nerve damage, or vascular disease)
  • ischaemic heart disease (heart disease caused by reduced blood flow in the blood vessels of the heart muscle)
  • a stroke
  • history of breast cancer
  • severe liver disease.
Emergency contraception should be taken as soon as possible after unprotected intercourse.
The effectiveness of this medicine may be reduced if you have any of the following conditions:
  • disease of your gastro-intestinal tract that interferes with the digestion and absorption of your food (such as Crohn's disease)
  • vomiting or severe diarrhoea.
If these conditions apply to you, your doctor may recommend taking another tablet.
If you are not sure whether you should take this medicine, talk to your doctor or pharmacist.
  1. You are currently pregnant, you think you may be pregnant or you plan to become pregnant. Do not take this medicine whilst pregnant. Do not take this medicine if you have missed your period as you may be pregnant.
  2. You are currently breastfeeding or you plan to breastfeed. Levonorgestrel has been identified in breast milk. Women should not breastfeed within 3 days of taking this medicine.
  3. You are planning to have surgery or an anaesthetic.
  4. You are currently receiving or are planning to receive dental treatment.
  5. You are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.
Some medicines may interact with levonorgestrel. These include:
  • barbiturates (including primidone), phenytoin, and carbamazepine, medicines which may be used to treat epilepsy
  • rifampicin and rifabutin, medicines used to treat tuberculosis
  • ritonavir and efavirenz, medicines used to treat HIV infection
  • griseofulvin, a medicine used to treat fungal infections
  • herbal medicines containing St John's Wort (Hypericum perforatum)
  • cyclosporin, a medicine used to prevent organ transplant rejection.
If you are taking any of these you may need a different dose of levonorgestrel or you may need to use a different method of emergency contraception.
Other medicines not listed above may also interact with levonorgestrel.

How to take this medicine

Follow carefully all directions given to you by your doctor or pharmacist. Their instructions may be different to the information in this leaflet.

Take the tablet as soon as possible after unprotected intercourse. The sooner that you take the tablet, the more effective the treatment is likely to be.

It is best to take it immediately after you receive it. The tablet should be taken no later than 72 hours after intercourse.

After taking this medicine

If you vomit within 2 hours of taking this tablet you should return to your pharmacy, doctor or clinic as the tablet may not be absorbed and you will need to take an additional tablet.

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively, go to the Accident and Emergency department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking this medicine

Things you must do

Tell your doctor that you have taken this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant (you must not take this medicine while pregnant)
  • you are breastfeeding or are planning to breastfeed (you should not breastfeed within 3 days of taking this medicine)
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.

This medicine is only intended as an emergency measure. If you have not already done so you should discuss with your doctor other methods of long-term contraception.

If you have taken this medicine, then it is recommended that you do not have sex again until you get your next period. If you do have sex, you should use a barrier method (e.g. condom, diaphragm, spermicide, cervical cap) until you get your next period.

You should see your doctor within 3 weeks of taking this medicine.

You may experience spotting or vaginal bleeding earlier or later than expected.

If you do not get your period within 3 weeks of taking this medicine you must see your doctor, as you may be pregnant.

If this medicine does not work, you could be pregnant. Your doctor will order a pregnancy test.

If you experience severe stomach pain you should see your doctor immediately as on rare occasions a tubal (ectopic) pregnancy could occur.

Tell any other doctors, dentists and pharmacists who are treating you that you have taken this medicine.

Things you must not do

Do not:

  • Take this medicine for any reason other than emergency contraception.
  • Give this medicine to anyone else.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

Possible side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking this medicine or if you have any questions or concerns.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor or pharmacist if you notice any of the following:

  • tiredness
  • nausea
  • vomiting
  • dizziness
  • stomach pain
  • diarrhoea
  • headache
  • tender breasts
  • increased vaginal bleeding
  • skin reactions.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell. Other side effects not listed above may occur in some patients.

Allergic reactions

If you think you are having an allergic reaction to this medicine, tell your doctor or pharmacist immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

  • cough, shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin
  • fainting
  • hayfever-like symptoms.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If you do not want to take this medicine or it has passed its expiry date, return it to your pharmacist for disposal.

Product description

What Postella-1 Tablet looks like

1.5 mg tablet - Round, biconvex, white tablet, engraved "C" on one side and "1" on the other side.

Pack size: 1 tablet only.

Ingredients

Each tablet contains 1.5 mg levonorgestrel as the active ingredient.

It also contains the following inactive ingredients:

  • microcrystalline cellulose
  • lactose monohydrate
  • croscarmellose sodium
  • poloxamer
  • magnesium stearate

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

Postella-1 1.5 mg tablet (blister pack): AUST R 231505.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

This leaflet was last updated in:
March 2021.

Published by MIMS May 2021

BRAND INFORMATION

Brand name

Postella-1

Active ingredient

Levonorgestrel

Schedule

S3

 

1 Name of Medicine

Levonorgestrel.

2 Qualitative and Quantitative Composition

Postella-1 is an emergency oral contraceptive tablet containing the synthetic progestogen, levonorgestrel.
The tablet contains 1.5 mg levonorgestrel as the active ingredient.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Round, biconvex, white tablet, engraved "C" on one side and "1" on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Emergency contraception within 72 hours of unprotected intercourse.
It should be used only as an emergency measure. Women who present for repeated courses of emergency contraception should be advised to consider long-term methods of contraception.

4.2 Dose and Method of Administration

Postella-1 tablet is intended for oral administration.

Dosage.

One 1.5 mg tablet to be taken as soon as possible (and not later than 72 hours) after unprotected intercourse.
The highest efficacy is achieved if the tablet is taken as early as possible. Therefore, treatment should not be delayed as efficacy declines with time.
If the patient vomits within two hours of taking the tablet, she should return to her pharmacist, doctor or clinic where an additional tablet may be given.
This medicine can be used at any time during the menstrual cycle unless menstrual bleeding is overdue.

Children.

Not recommended for administration to children.
Only limited data are available in young women of child-bearing potential aged 14 - 16 years. No data are available about use in young women aged less than 14 years or children.

4.3 Contraindications

Hypersensitivity to the active substance levonorgestrel or any of the excipients.
This medicine should not be given to pregnant women. If menstrual bleeding is overdue, if the last menstrual period was abnormal in timing or character, or if pregnancy is suspected for any other reason, pregnancy should be excluded (by pregnancy testing or pelvic examination) before treatment is given.
If a woman has had unprotected intercourse more than 72 hours earlier in the same menstrual cycle conception may have already occurred. Treatment with this medicine following the second act of intercourse during same menstrual cycle may therefore be ineffective in preventing pregnancy. While the consensus is that levonorgestrel is not teratogenic, no guarantee can be given that pregnancy will result in a normal baby.
Progestogen-only contraceptive pills are used as a routine method of birth control over longer periods of time and are contraindicated in some conditions. It is not known whether these same conditions apply to the levonorgestrel regimen consisting of the emergency use of one 1.5 mg tablet.
Traditionally many of the contraindications to combined hormonal contraception have been applied to progestogen-only contraception. Since the contraindications largely apply to oestrogen, this is inappropriate. In their Medical Eligibility Criteria, the World Health Organisation advises that the only absolute contraindications to high-dose progestogen-only contraception are unexplained vaginal bleeding, current breast cancer, pregnancy or hypersensitivity to any of the ingredients of the preparation.

4.4 Special Warnings and Precautions for Use

Conditions which are regarded as relative contraindications include severe hypertension (BP > 180+/110+), diabetes mellitus with nephropathy, retinopathy, neuropathy or vascular disease, ischaemic heart disease, stroke or a past history of breast cancer. Since exposure to levonorgestrel with this medicine is brief, the risks of pregnancy in all women, including those with pre-existing medical conditions, are almost certainly greater than those associated with this medicine. In individual cases the risk-benefit ratio should be assessed by the practitioner in discussion with the patient.
This medicine is not recommended in patients with severe hepatic dysfunction.
This medicine is not as effective as conventional regular methods of contraception and is suitable only as an emergency measure. Emergency contraception does not prevent a pregnancy in every instance. If menstrual periods are delayed by more than 5 days or abnormal bleeding occurs at the expected date of menstrual periods or pregnancy is suspected for any other reason, pregnancy should be excluded.
If pregnancy occurs after treatment with levonorgestrel, the possibility of an ectopic pregnancy should be considered. The absolute risk of ectopic pregnancy is likely to be low, as levonorgestrel prevent ovulation and fertilisation. Ectopic pregnancy may continue, despite the occurrence of uterine bleeding. Therefore, levonorgestrel is not recommended for patients who are risk of ectopic pregnancy. (previous history of salpingitis or of ectopic pregnancy).
Repeated administration within a menstrual cycle is not advisable. Women who present for repeated courses of emergency contraception should be advised to consider a long-term method of contraception.
Emergency contraception should be taken as soon as possible after unprotected sexual intercourse or failure of a contraceptive method.
Emergency contraception does not protect against sexually transmitted diseases (STDs) including HIV/AIDS.

Precautions before use.

Exclude pregnancy if suspected clinically.
Breast or pelvic examinations are not routinely necessary. Perform such examinations only if indicated by the patient's history.
Blood pressure may be measured before prescribing this medicine. An elevated BP is not a contraindication to treatment but indicates the need for further investigation.
No routine laboratory testing is required.
Possibility of an early or late onset of the next menstrual period.
Advise the practice of abstinence or careful use of a barrier method (e.g. condom, diaphragm, spermicide, cervical cap) until the onset of the next period. Follow-up should be offered 3 weeks after administration of therapy to assess the effectiveness of the method, to discuss future management if a period has not occurred, and to counsel the patient about future contraception. The use of levonorgestrel does not contraindicate the continuation or starting of regular hormonal contraception.
Women should be warned that if pregnancy occurs after treatment with this medicine, there is a possibility of an ectopic pregnancy.

Precautions after use.

If pregnancy occurs after treatment with this medicine, the possibility of an ectopic pregnancy should be considered.
Vomiting, severe diarrhoea or other causes of malabsorption, such as Crohn's disease, might impair the efficacy of this medicine. Women suffering from conditions associated with possible malabsorption should be referred for medical consultation as consideration should be given to the taking of another tablet.
If the patient vomits within two hours of taking the tablet, she should return to her pharmacist, doctor or clinic where an additional tablet may be given (also see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

Not indicated for use in children.
Only limited data are available in young women of child-bearing potential aged 14 - 16 years. No data are available about use in young women aged less than 14 years or in children (see Section 4.2 Dose and Method of Administration).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The metabolism of levonorgestrel can be enhanced by concomitant use of drugs which induce CYP3A4, one of the family of liver enzymes. This may reduce the effectiveness of this medicine in preventing pregnancy. Concomitant use of liver enzyme inducers like efavirenz, rifampin and medicinal products for epilepsy is not recommended.
Medicines suspected of having the capacity to reduce the efficacy of levonorgestrel-containing medications include barbiturates (including primidone), phenytoin, carbamazepine, herbal medicines containing Hypericum perforatum (St John's wort), rifampicin, rifabutin, ritonavir, efavirenz and griseofulvin.
Medicines containing levonorgestrel may increase the risk of cyclosporin toxicity due to possible inhibition of cyclosporin metabolism.
Levonorgestrel has the ability to decrease glucose tolerance when it is used in the longer term. However, use of levonorgestrel as an emergency contraceptive is not thought to induce significant modification of carbohydrate metabolism.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Levonorgestrel increases the possibility of cycle disturbances which can sometimes lead to earlier or later ovulation date. These changes can result in modified fertility date; however, there are no long-term fertility data.
(Category D)
This medicine is not to be used during an existing or suspected pregnancy. Research has found no significant effects on foetal development associated with the long-term use of contraceptive doses of combined oral steroids before pregnancy or taken inadvertently during early pregnancy. There have been an insufficient number of pregnancies in patients using levonorgestrel-only oral contraceptives to rigorously evaluate the potential for developmental toxicity; however, based on the combined oral contraceptive experience, an increase in abnormalities is not expected. If taken by the mother at or after 8 weeks post-conception, progestogens such as levonorgestrel can cause virilisation of the female foetus. This is a dose dependent effect. Prior to 8 weeks post-conception, they have no virilising effects. There are no studies of the effect of the high levonorgestrel doses used in this medicine on pregnancy and embryo/foetal development.
 Progestogens do not appear to affect the quantity or quality of breast milk. However, levonorgestrel has been identified in the breast milk following oral administration to lactating women. Women should be advised not to breast-feed within 3 days after taking this medicine.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

The adverse reactions reported with an incidence of greater than 1% in the Ho and Kwan and the Pivotal Studies (two 750 microgram tablets taken 12 hours apart) are included in Table 1.
Side effects did not result in any discontinuations in either study. No ectopic pregnancies or congenital abnormalities were reported in either study. However, such a possibility must always be considered, as there have been rare reports of ectopic pregnancies reported during post-marketing surveillance. Cutaneous reactions have also been reported from post-marketing surveillance on rare occasions.
In the additional studies conducted to compare dosing with two 750 microgram tablets taken as a single dose and taking the two tablets 12 hours apart, the adverse events recorded were mostly similar to the above studies, as detailed in Table 2.
One ectopic pregnancy was observed in the pivotal study and none in the supporting (Arowojolu et al, 2002) study.
Overall, there was no indication that taking the entire 1.5 mg dose at the one time resulted in an adverse event profile of greater concern than that for the regimen when the two 750 microgram tablets were taken 12 hours apart.
From post-marketing surveillance additionally, the following adverse events have been reported:

Skin and subcutaneous tissue disorders.

Very rare (< 1/10,000): rash, urticarial, pruritus.

Reproductive system and breast disorders.

Very rare (< 1/10,000): pelvic pain, dysmenorrhoea.

Gastrointestinal disorders.

Very rare (< 1/10,000): abdominal pain.

General disorders and administration site conditions.

Very rare (< 1/10,000): face oedema.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives. Overdose may cause nausea, and withdrawal bleeding may occur. There are no specific antidotes and treatment should be symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The precise mode of action of levonorgestrel is not known. Emergency hormonal contraception is thought to work mainly by preventing ovulation and fertilisation by altering tubal transport of sperm and/or ova. It may also cause endometrial changes that discourage implantation. Levonorgestrel is not effective once the process of implantation has begun.

Efficacy.

From earlier studies where two levonorgestrel tablets (each containing 750 microgram levonorgestrel) have been taken 12 hours apart, it has been estimated that 85% of expected pregnancies are prevented. Efficacy appears to decline with time after intercourse (95% within 24 hours, 85% 24 - 48 hours, 58% if used between 48 and 72 hours).
In an additional study to compare taking the two tablets 12 hours apart versus taking a total dose of 1.5 mg after unprotected intercourse, similar rates of prevention of pregnancy were observed when taken within 72 hours. In this study, it was also observed that efficacy declined with increasing time of taking the medication after intercourse.
In further studies to compare the bioavailability of the single 1.5 mg tablet to two 750 microgram tablets, it has been determined that the efficacy would be similar.

Clinical trials.

Two large controlled studies of levonorgestrel using 750 microgram tablets (two tablets taken 12 hours apart) for emergency contraception have been undertaken. The first of these is referred to as the Ho and Kwan study and the second, which included larger numbers, as the Pivotal study. Both studies compared this treatment regimen to the Yuzpe regimen (ethinyloestradiol 100 microgram plus levonorgestrel 500 microgram, repeated 12 hours later).
The Ho and Kwan study was single-centre and open-label (age range 18 - 45 years) while the Pivotal study was multi-centre, randomised and double-blind (age range 14 - 47 years), with both including women requiring emergency contraception resulting from no contraception used during intercourse or contraception method failure. The regimens were similar with two exceptions:
The Ho and Kwan study allowed treatment to be initiated up to 48 hours post-intercourse, whereas the Pivotal study allowed a 72-hour gap between treatment initiation and intercourse.
The treatment regimen in both studies used two tablets, the second taken 12 hours after the first. In the Pivotal study only, women in each of the two groups were provided with replacement medication to take should vomiting occur within four hours of either dose.
The efficacy results from the efficacy population analysis from the two studies are summarised in Table 3.
The relative risk of pregnancy in the Pivotal study for the Yuzpe versus levonorgestrel regimens was 2.8 with a lower one-sided 95% confidence bound of 1.53.
Stratified analyses of the data showed no significant effect for age or ethnicity. For interval between intercourse and initiation of treatment, shorter intervals were associated with lower pregnancy rates.
Two further studies have been conducted in order to determine whether taking two 750 microgram tablets at the same time (as a single dose) was as efficacious as taking the two tablets 12 hours apart.
The pivotal study for this comparison was a double-blind, randomised, double-dummy, multi-centre study, conducted by the WHO/HRP across 10 countries. This study included women ranging in age from 14 to 52 year, and allowed for enrolment up to 120 hours after intercourse.
A supporting study (Arowojolu et al, 2002) for this comparison was conducted in Nigeria at a single centre. A total of 1118 women were assessed for efficacy in this study.
The efficacy results from the data analysis for the two treatment regimens from both studies are summarised in Table 4.
There was no significant difference in efficacy between the two levonorgestrel treatment groups in the pivotal study. Shorter intervals between intercourse and treatment were associated with lower pregnancy rates in both groups.
The authors of the supporting study (Arowojolu et al, 2002) concluded that both treatment regimens were effective - the single two tablet dose appeared to be more effective than when the two tablets were taken 12 hours apart and that the earlier the medication is taken after unprotected intercourse, the better the efficacy.
Adverse events reported in these two studies were similar for both treatment groups (see Section 4.8 Adverse Effects (Undesirable Effects)).
No specific clinical trials investigating pregnancy outcome have been conducted on the single 1.5 mg tablet. Evidence for its efficacy is based on the 1.5 mg tablet and two 750 microgram tablets taken at the same time having the same pharmacokinetic profile.

5.2 Pharmacokinetic Properties

Absorption.

A study compared the pharmacokinetics of one 1.5 mg levonorgestrel tablet taken as a single dose with that of two 750 microgram levonorgestrel tablets taken 12 hours apart. Following ingestion of one 1.5 mg tablet, maximum plasma drug levels of 18.5 nanogram/mL were found at 2 hours. Thereafter, levonorgestrel plasma levels decreased with a half-life of approximately 26 hours. In this study, the Cmax was higher for the single 1.5 mg tablet, but plasma levels over a 24-hour period were similar, as were the Tmax and half-life.
In another study, a comparison of the pharmacokinetics with two 750 microgram tablets taken together (as a single dose) or 12 hours apart showed similar levels of serum levonorgestrel over a 24-hour period, and similar terminal half-lives (43.7 versus 43.3 hours). The Cmax was about 50% higher when the two tablets were taken together than when they were taken 12 hours apart (12.3 versus 7.9 nanogram/mL, p = 0.03), and this occurred at 2.5 and 1.8 hours, respectively, after the (first) dose.
When the bioavailability of a single 1.5 mg tablet was compared to two 750 microgram tablets taken at the same time, AUC and Cmax were found to be the same with both treatments. In this study, maximum plasma drug level of 19.1 nanogram/mL was found at 1.7 hours following the ingestion of one 1.5 mg tablet. Thereafter, levonorgestrel plasma levels decreased with a half-life of approximately 27 hours.
In general, it is recognised that the pharmacokinetics of levonorgestrel can be quite variable.
The absolute bioavailability of levonorgestrel was determined to be almost 100% of the dose administered.

Distribution.

Levonorgestrel is bound to serum albumin and sex hormone binding globulin (SHBG). Only about 1.5% of the total serum levels are present as free steroid, but 65% are specifically bound to SHBG.

Metabolism and excretion.

Levonorgestrel is not excreted in unchanged form but as metabolites. Levonorgestrel metabolites are excreted in about equal proportions in urine and faeces. The biotransformation follows the known pathways of steroid metabolism with levonorgestrel being hydroxylated in the liver and the metabolites then excreted as glucuronide conjugates. No pharmacologically active metabolites are known.
About 0.1% of the maternal dose can be transferred via milk to the breast-fed infant.

5.3 Preclinical Safety Data

Genotoxicity.

No studies of the mutagenic potential of levonorgestrel have been performed.

Carcinogenicity.

No studies of the carcinogenic potential of levonorgestrel have been performed. Numerous epidemiological studies have been performed to determine the incidence of breast, endometrial, ovarian and cervical cancer in women using combination oral contraceptives (COCs). Some studies suggest that COC use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women, but there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behaviour and other factors such as human papilloma virus. Evidence in the literature suggests that use of COCs is not associated with an increased risk of developing breast cancer in the overall population of users. However, some of these same studies have shown an increased relative risk of breast cancer in certain subgroups of COC users, although no consistent pattern of findings has been identified. Benign hepatic adenomas have been found to be associated with the use of oral contraceptives containing levonorgestrel. Although benign, hepatic adenomas may rupture and cause death through intra-abdominal haemorrhage. The contribution of the progestin component of oral contraceptives to the development of hepatic adenomas is not known.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, poloxamer, magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Blister pack (PVC/PVdC/Al) of 1 tablet: AUST R 231505.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Levonorgestrel is a white or almost white, odourless or almost odourless, crystalline powder. It is practically insoluble in water; slightly soluble in alcohol, acetone, and ether; soluble in chloroform; and sparingly soluble in methylene chloride.

Chemical structure.


Chemical Name: 13-ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one.
Molecular Formula: C21H28O2.
Molecular Weight: 312.45.

CAS number.

797-63-7.

7 Medicine Schedule (Poisons Standard)

S3 - Pharmacist Only Medicine.

Summary Table of Changes