Levonorgestrel

Registered South African indications:

• Contraception

Contraindications

• Hypersensitivity to levonorgestrel or to any of the excipients
• Known or suspected pregnancy
• Presence or history of hepatic disease as long as liver function values have not returned to normal (active liver disease)
• History of or existing thromboembolic processes (e.g. stroke, myocardial infarction, previous proven deep-vein thrombosis (DVT), previous pulmonary embolism, and inherited thrombophilia)
• Presence or history of liver tumours (benign or malignant)
• Depression not well controlled with treatment
• A history of depression with the use of hormonal contraceptives
• Undiagnosed abnormal vaginal bleeding
• Severe diabetes with vascular changes
• Recurrent cholestatic jaundice or markedly impaired liver function
• Hormone-dependent neoplasms (e.g. current or personal and family history of breast cancer)
• History of non-cancerous breast diseases (atypical hyperplasia or lobular carcinoma in situ)
• Severe migraine or cerebrovascular insufficiency
• Patients known with inherited genetic mutations: BRCA1 and BRCA2 genes
• Early menstrual periods (before the age of 12 years)
• Previous treatment using radiation therapy to the chest or breast
• Previous exposure to diethylstilbestrol (DES)
• Relative contraindications include a history of diabetes mellitus, epilepsy, asthma, hypertension, depression, or states in which fluid retention occurs
• Medication should be discontinued immediately if migraine becomes focal, or there is a loss of vision, or if there is an onset of unexplained chest pain

Cautions

• Pregnancy
• Hypertension
• Prolonged treatment
• Diabetes mellitus
• History of ectopic pregnancy
• History of chloasma gravidarum
• Risk factors for venous thromboembolism
• Galactose intolerance
• Lapp lactase deficiency
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase deficiency

Forms avail. in SA and covered in this monograph: tab

Contraception

• Oral (tab): 30μg, dly at the same time every day continuously

Initiate on day 1 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

Mechanical contraceptive methods should be used for the first 14 days after initiating

See additional prescribing points

Not indicated for use in premenarchal children

Pregnancy

• Contraindicated
• The administration of levonorgestrel during pregnancy is contraindicated. If pregnancy occurs during medication with levonorgestrel the preparation is to be withdrawn immediately. Epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used oral contraceptives prior to pregnancy, nor a teratogenic effect when oral contraceptives were taken inadvertently during early pregnancy

Breastfeeding

• Compatible
• Hormonal contraceptives are not recommended as the contraceptive method of first choice during breastfeeding, but progestogen-only methods are considered to comprise the next choice category after non-hormonal methods. Levonorgestrel can be used by breastfeeding women as there appears to be no evidence to suggest that progestogen-only pills have a detrimental effect on breast milk or infant growth or development
•  A breastfeeding woman can start a progestogen-only treatment, up to 21 days post-partum without the need for additional contraceptive protection. 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 levonorgestrel use or the woman has to wait for her first menstrual period

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depressed mood
• Migraine
• Headache
• Dizziness

Gastrointestinal Disorders

• Nausea and vomiting

Genitourinary Disorders

• Changes in vaginal bleeding pattern
• Decreased or increased libido

Endocrine and Metabolic Disorders

• Increased or decreased weight

Immune, Blood and Lymphatic System Disorders

• Allergic reaction

• CYP450 inducers
• Ciclosporin
• Lamotrigine
• Warfarin
• Phenindione

• Blood pressure

Specific cases may require

• Breast examination
• Gynaecological examination
• Cervical cytology

Changing from different contraceptive methods

• Changing from a combined oral contraceptive (COC): The first tablet of levonorgestrel should be taken on the 1st day after the last active tablet of the COC pack. Additional contraceptive precautions are not required. 
• Changing from a progestogen-only parenteral method (implant, injection): The switch should be made before or when the next injection or implant is due.

Initiating in special circumstances

• Post-partum use: Initiated up to 21 days post-partum (no additional contraceptive is required). If started after 21 days additional barrier contraceptive methods should be used for 7 days. However, if intercourse has already occurred, pregnancy should be excluded before the starting or the woman has to wait for her 1st menstrual period.
• Post-abortion or miscarriage use after a first trimester abortion, levonorgestrel may be started at the time of the abortion or miscarriage. Additional contraceptive precautions will not then be required. If started after this time barrier contraceptive methods should be used for 7 days.

Special circumstances requiring additional contraception

• Gastrointestinal disturbances:  If vomiting occurs within 2 hours of taking a tablet, another pill should be taken as soon as possible. If a replacement pill is not taken within 3 hours of the scheduled time, additional, barrier contraceptive methods should be used for 7 days. 
• In cases of persistent vomiting and/or very severe diarrhoea, additional barrier contraceptive methods should be used during the illness and for 7 days after recovery.

Missed dose

• Management of missed pills: If the user forgets a pill she should take it as soon as she remembers and carry on with the next pill at the same time. If the pill was more than 3 hours overdue she should continue normal pill taking but must also use barrier contraceptive methods for the next 7 days.

Tablet 30μg - EML (Primary)

Levonorgestrel binds to progesterone and oestrogen receptors in the female reproductive tract, breasts, hypothalamus and pituatary. The net effect of binding to these receptors is decreased release of gonadotropin releasing hormone from the hypothalamus and blunting of the pre-ovulatory luteinizing hormone surge. It also has a number of local effects which include thickening of cervical mucous (which hinders sperm passage to the uterus) and alterations to the endometrium which may affect implantation.

Tablet 30μg

• Microval (Pharmacare) originator
• Hy-an (Mylan)

Also available in the following forms: Tablet (emergency contraceptive) and intra-uterine device.