POSTINOR®-2
Levonorgestrel 750 mcg
tablets
Presentation
Each round white tablet contains 750
micrograms of levonorgestrel.
Uses
Actions
The precise mode of action of
Postinor-2 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.
Efficacy
It has been estimated that Postinor-2
prevents 85% of expected pregnancies. Efficacy appears to decline with time
after intercourse (95% within 24 hours, 85% if used between 24 and 48 hours
and/or 58% if used between 48 and 72 hours). Efficacy after 72 hours is
unknown.
Pharmacokinetics
Orally administered levonorgestrel is
rapidly and almost completely absorbed. Following ingestion of one tablet of
Postinor-2, maximum drug serum levels of 14.1 ng/ml were found at 1.6 hours.
Thereafter, levonorgestrel serum levels decrease in two disposition phases with
mean elimination half-lives which range from about 9 hours to 14.5 hours.
Levonorgestrel is not excreted in unchanged form but as metabolites.
Levonorgestrel metabolites are excreted in about equal proportions with urine
and faeces. The biotransformation follows the known pathways of steroid
metabolism. No pharmacologically active metabolites are known.
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. The absolute bioavailability of levonorgestrel was determined to be almost
100% of the dose administered.
About 0.1% of the maternal dose can
be transferred via milk to the nursed infant.
Indications
Postinor-2 is an oral emergency
contraceptive indicated for use 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.
Dosage and
Administration
One 750 microgram tablet to be taken
as soon as possible (and not later than 72 hours) after unprotected intercourse,
followed by one additional 750 microgram tablet 12 hours after the first
dose.
The highest efficacy is achieved if
the first dose is started as early as possible. Therefore, treatment should not
be delayed as efficacy declines with time. However, since it is critical that
the second dose is taken 12 hours after the first, the first dose may be taken
at a time which would enable the patient to take the second dose at a time
convenient to her.
If the patient vomits within two
hours of taking the pills, she should return to her doctor or clinic where an
additional pill may be given.
Postinor-2 can be used at any time
during the menstrual cycle unless menstrual bleeding is overdue.
Children
Postinor-2 is not recommended in
children. Limited data is available in young women of child-bearing potential
aged 14 and over.
Contraindications
Postinor-2 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 Postinor-2 following the second act of
intercourse 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
(POPs) 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 Postinor-2 regimen consisting of the emergency use
of two pills.
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.
Warnings and
Precautions
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 Postinor-2 is brief, the risks of pregnancy in
all women, including those with pre-existing medical conditions, are almost
certainly greater than those associated with Postinor-2. In individual cases,
the risk-benefit ratio should be assessed by the practitioner in discussion with
the patient.
Postinor-2 is not as effective as
conventional regular methods of contraception and is suitable only as an
emergency measure. Women who present for repeated courses of emergency
contraception should be advised to consider a long-term method of
contraception.
Emergency contraception does not
protect against sexually transmitted infections.
Further precautions for
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 (BP) may be measured
before prescribing Postinor-2. An elevated BP is not a contraindication to
treatment but indicates the need for further investigation.
No routine laboratory testing is
required.
Explain the importance of follow-up
and the possibility of an early or late onset of the next menstrual period to
the patient. Advise the practice of abstinence or careful use of a barrier
method 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.
If pregnancy occurs after treatment
with Postinor-2, 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
Postinor-2. Consideration should be given to the taking of more pills.
Effect on ability to drive and use
machines
No effect is known.
Preclinical safety
data
In acute toxicity studies performed
in mice and rats levonorgestrel induced a decrease of body weight and
dermatitis-like (non-irritative or non-allergic) changes on the skin.
In repeat dose toxicity studies
performed in mice, rats and rabbits, there were no overt signs of toxicity and
no target organs or functions were identified other than the reproductive
system. These toxic effects observed on the reproductive system (stillbirth,
fetotoxicity or changes in fertility index) can be regarded as an extreme
manifestation of pharmacological effect of levonorgestrel due to the changes of
hormone regulation.
Pregnancy and lactation
Use in Pregnancy
Postinor-2 should not be given to
pregnant women. The effect of Postinor-2 on the foetus is unknown. Some
investigators have suggested that sex hormones taken in the first trimester of
pregnancy may slightly increase the risk of foetal malformations, but others
have failed support these findings. The consensus opinion amongst teratologists
is that known teratogens will not produce malformations before organogenesis
starts, which is later than 72 hours after fertilisation.
Use in Lactation
There is no evidence that Postinor-2
taken only in an emergency situation diminishes the yield of breast milk.
However, minute amounts of the active substance are excreted with the
milk.
Adverse Effects
Nausea occurs in about 25% of women
taking Postinor-2 and vomiting occurs in about 5% of women taking
Postinor-2.
Bleeding patterns may be temporarily
disturbed, but most women will have their next menstrual period at the expected
time.
Some women may experience bleeding or
spotting after taking Postinor-2 and some may experience early or delayed onset
of menses. If the next menstrual period is more than 7 days overdue pregnancy
should be excluded.
Other side effects include breast tenderness, headache, dizziness and fatigue
.
