Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2017 Publisher: Bayer New Zealand Limited, 3 Argus Place, Hillcrest, North Shore, AUCKLAND 0627 Free Phone: 0800 233 988
Pharmacotherapeutic group: Progestogens, levonorgestrel
ATC Code: G03AC03
MICROLUT contains the oral progestogen levonorgestrel in a very low dose. The continuous daily ingestion of 0.03mg levonorgestrel prevents conception in several independent ways. Mainly, there are changes in the cervical mucus which make the migration and ascent of sperm difficult or block this. Furthermore, changes in the endometrium throughout the cycle can be considered as having the effect of rendering nidation difficult. Ovulation is not inhibited in the majority of women, but MICROLUT can impair the midcycle gonadotrophin peaks and the corpus luteum function which may contribute to the contraceptive action.
Orally administered levonorgestrel is rapidly and completely absorbed. Peak serum concentrations of 0.8 ng/ml are reached about 1 hour after single ingestion of MICROLUT. The absolute bioavailability of levonorgestrel from MICROLUT is about 82%.
Levonorgestrel is bound to serum albumin and to sex hormone-binding globulin (SHBG). Only about 1.5% of the total serum drug concentrations is present as free steroid and about 65% is specifically bound to SHBG. The relative distribution (free, albumin-bound, SHBG-bound) depends on the SHBG concentrations in the serum. Under MICROLUT treatment, a slight decline in the SHBG serum levels could occur which in turn might have minor effects on the relative distribution of levonorgestrel with respect to the two binding proteins. The apparent volume of distribution of levonorgestrel is about 106 l.
Levonorgestrel distributes into mother’s milk and about 0.1% of the maternal dose can be transferred to the breast-fed infant.
Levonorgestrel is completely metabolised by the known pathways of steroid metabolism. No pharmacologically active metabolites are known. The metabolic clearance rate from serum is between 1 and 1.5ml/min/kg.
Levonorgestrel serum levels decrease in two phases which are characterised by halflives of about 1 hour and about 20 hours, respectively. Levonorgestrel is not excreted in unchanged form. Its metabolites are excreted at about equal parts via urine and faeces. The half-life of metabolite excretion is about 1 day.
Following daily repeated administration of levonorgestrel, drug serum levels reach steady-state after about 2-3 weeks, when SHBG levels achieve steady-state. The pharmacokinetics of levonorgestrel is influenced by serum levels of SHBG. The daily ingestion of 0.15mg levonorgestrel (corresponding to 5 times the daily dose of MICROLUT) led to a 50% decrease in SHBG serum levels and thus, a 40% reduction in levonorgestrel trough levels after 2-3 weeks. A similarly directed effect of MICROLUT should account, however, for a decrease of only about 10% in both parameters.
Acute toxicity studies did not indicate a risk of acute adverse effects in case of inadvertent intake of a multiple of the daily contraceptive dose.
In animal studies on systemic tolerance with repeated oral administration, including tumourigenic studies, no systemic intolerance reactions were observed which would cause concern regarding the dosages required for contraception. However, it should be borne in mind that sex steroids might stimulate the growth of hormone-dependent tissues and tumours.
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