Drugs List

Therapeutic Indications

Uses

Infertility due to inadequate luteal phase

IVF: infertility due to tubal, idiopathic or endometriosis linked sterility with normal ovulatory cycles

Administration

Vaginal use only.

The gel is applied directly from the specially designed sealed applicator into the vagina. The applicator should be removed from the sealed wrapper. The twist-off cap should not be removed at this time.

1. The applicator should be gripped firmly by the thick end. It should be shaken down like a thermometer to ensure that the contents are at the thin end.

2. The tab should be twisted off and discarded.

3. The applicator may be inserted while patient is in a sitting position or when lying on her back with the knees bent. The thin end of applicator should be gently inserted well into the vagina.

4. The thick end of the applicator should be pressed firmly to deposit gel. The applicator should be removed and discarded in a waste container.

Contraindications

Missed / incomplete abortion
Undiagnosed vaginal bleeding
Porphyria
Breastfeeding
Concurrent intravaginal therapy
History of liver tumours and known or suspected progesterone-sensitive malignant tumours
Genital or breast cancer
Severe arterial disease
History during pregnancy of idiopathic jaundice
History during pregnancy of severe pruritis
History during pregnancy of pemphigoid gestationis
Current or history of thrombophlebitis
Current or history of thromboembolic disorder
Current or history of cerebrovascular accident

Precautions and Warnings

Use with caution in the following:

Severe hepatic impairment
Renal impairment
Patients with risk factors for thromboembolism, such as personal or family history.
Diabetes (Progestogens may decrease glucose tolerance. Monitor diabetes mellitus patients closely).
Disorders aggravated by fluid retention i.e.
Epilepsy
Hypertension
Migraine
Asthma
Cardiac dysfunction

In cases of undiagnosed breakthrough bleeding adequate diagnostic measures should be undertaken.

Monitor for signs of fluid retention.

Monitor hepatic function.

The excipient sorbic acid may cause local skin reactions i.e. contact dermatitis or vaginal irritation.

Warn patient that hirsutism may occur.

Perform a pre-treatment physical examination including breast and pelvic organs, as well as Papanicolaou smear.

Patients who have risk factors for thrombotic disorders should be kept under careful observation. Discontinue if thrombotic disorders occur or are suspected.

Patients who have a history of depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

Pregnancy and Lactation

Pregnancy

Contraindicated if there is a history during pregnancy of idiopathic jaundice, severe pruritis or pemphigoid gestationis.

In case of corpus luteum deficiency, progesterone may be used during the first month of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

Cases of gynaecomastia have been reported but these are extremely rare. The direct effect of progesterone therapy on the nursing infant is generally unknown, but it is believed minimal to none because natural progesterone is poorly bioavailable to the infant via milk (Hale). Progesterone is not expected to cause any adverse effects in breastfed infants or have any detrimental effects on milk production. Nonetheless the manufacturer states it should be contraindicated.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

"Spotting" bleeding
Intermenstrual bleeding
Menstrual disturbances
Bloating
Premenstrual symptoms
Fluid retention
Breast tenderness
Weight changes
Nausea
Dizziness
Depression
Skin reactions
Pruritus
Urticaria
Rash
Acne
Hirsutism
Alopecia
Jaundice
Anaphylaxis
Decreased glucose tolerance
Insomnia
Changes in libido
Vaginal irritation
Burning sensation

Presentation

Vaginal gel containing 8% progesterone equivalent to 90 mg per dose.

Drugs List

Therapeutic Indications

Uses

Infertility due to inadequate luteal phase

IVF: infertility due to tubal, idiopathic or endometriosis linked sterility with normal ovulatory cycles

Dosage

Each applicator delivers 1.125 g of gel.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

Vaginal use only.

The gel is applied directly from the specially designed sealed applicator into the vagina. The applicator should be removed from the sealed wrapper. The twist-off cap should not be removed at this time.

1. The applicator should be gripped firmly by the thick end. It should be shaken down like a thermometer to ensure that the contents are at the thin end.

2. The tab should be twisted off and discarded.

3. The applicator may be inserted while patient is in a sitting position or when lying on her back with the knees bent. The thin end of applicator should be gently inserted well into the vagina.

4. The thick end of the applicator should be pressed firmly to deposit gel. The applicator should be removed and discarded in a waste container.

Contraindications

Missed / incomplete abortion
Undiagnosed vaginal bleeding
Porphyria
Breastfeeding
Concurrent intravaginal therapy
History of liver tumours and known or suspected progesterone-sensitive malignant tumours
Genital or breast cancer
Severe arterial disease
History during pregnancy of idiopathic jaundice
History during pregnancy of severe pruritis
History during pregnancy of pemphigoid gestationis
Current or history of thrombophlebitis
Current or history of thromboembolic disorder
Current or history of cerebrovascular accident

Precautions and Warnings

Use with caution in the following:

Severe hepatic impairment
Renal impairment
Patients with risk factors for thromboembolism, such as personal or family history.
Diabetes (Progestogens may decrease glucose tolerance. Monitor diabetes mellitus patients closely).
Disorders aggravated by fluid retention i.e.
Epilepsy
Hypertension
Migraine
Asthma
Cardiac dysfunction

In cases of undiagnosed breakthrough bleeding adequate diagnostic measures should be undertaken.

Monitor for signs of fluid retention.

Monitor hepatic function.

The excipient sorbic acid may cause local skin reactions i.e. contact dermatitis or vaginal irritation.

Warn patient that hirsutism may occur.

Perform a pre-treatment physical examination including breast and pelvic organs, as well as Papanicolaou smear.

Patients who have risk factors for thrombotic disorders should be kept under careful observation. Discontinue if thrombotic disorders occur or are suspected.

Patients who have a history of depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

Pregnancy and Lactation

Pregnancy

Contraindicated if there is a history during pregnancy of idiopathic jaundice, severe pruritis or pemphigoid gestationis.

In case of corpus luteum deficiency, progesterone may be used during the first month of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

Cases of gynaecomastia have been reported but these are extremely rare. The direct effect of progesterone therapy on the nursing infant is generally unknown, but it is believed minimal to none because natural progesterone is poorly bioavailable to the infant via milk (Hale). Progesterone is not expected to cause any adverse effects in breastfed infants or have any detrimental effects on milk production. Nonetheless the manufacturer states it should be contraindicated.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise patients to report breakthrough bleeding.

Advise patient of thromboembolic symptoms and to report them if they occur.

Side Effects

"Spotting" bleeding
Intermenstrual bleeding
Menstrual disturbances
Bloating
Premenstrual symptoms
Fluid retention
Breast tenderness
Weight changes
Nausea
Dizziness
Depression
Skin reactions
Pruritus
Urticaria
Rash
Acne
Hirsutism
Alopecia
Jaundice
Anaphylaxis
Decreased glucose tolerance
Insomnia
Changes in libido
Vaginal irritation
Burning sensation

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store below 25 degrees C.

Further Information

Last Full Review Date: May 2011

Reference Sources

British National Formulary, 61st Edition (2011) Pharmaceutical Press, London.

Martindale: The Complete Drug Reference, 36th edition (2009) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Crinone 8% Progesterone Vaginal Gel. Merck Serono Ltd. Revised December 2020.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Progesterone. Last revised: July 29, 2010
Last accessed: May 13, 2011