Female Sex Hormones- Progestin Drugs

Name of the Progestin Drugs

1. Desogestrel
2. Drospirenone
3. Etonogestrel
4. Medroxyprogesterone
5. Levonorgestrel
6. Norgestrel
7. Progesterone

Therapeutic Action

• Transform the proliferative endometrium into a secretory endometrium. They also inhibit the secretion of FSH and LH.
• Prevent follicle maturation and ovulation as well as uterine contraction.
• Exact mechanism of action in its function as a contraceptive is not known but it it thought that circulating progestins and estrogens “trick” the hypothalamus and pituitary and prevent the release of gonadotropin-releasing hormone (GnRH), FSH, and LH. Therefore, follicle development and ovulation are prevented.

Mechanism of Action:

Desogestrel enters the cell passively and acts by binding selectively to the progesterone receptor and generating low androgenic activity. Its binding produces an effect like a transcription factor and thus, it produces modifications in the mRNA synthesis.

Desogestrel works by thickening the mucus in the cervix to stop sperm reaching an egg to fertilise it. It can also stop ovulation – other mini pills that don’t contain the active ingredient desogestrel don’t do this.

Indications:

Oral contraception
Oral desogestrel is used in combination with ethinyl-estradiol as a contraceptive agent for the prevention of pregnancy. Desogestrel is part of the combined oral contraceptives that contain a mix of estrogen and progestin which inhibit ovulation.

Contraindications & Cautions:

• Active venous thromboembolic disorder.
• Do not use Desogestrel if you are pregnant or think you may be pregnant.
• Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
• Known or suspected sex-steroid sensitive malignancies.
• Hormone-sensitive cancers (e.g., breast cancer)
• Undiagnosed vaginal bleeding.
• Hypersensitivity to the active substance, soya, peanut and any contents of the medicine.

Metabolism and Half- Life:

• After oral administration, desogestrel is rapidly absorbed and it reaches a peak concentration of 2 ng/ml after 1.5 hours.
• Bioavailability: 60-80%.
• Desogestrel is rapidly metabolized in the intestinal mucosa and by first-pass hepatic metabolism to form the major metabolite of desogestrel is etonogestrel which is the biologically active metabolite.
• Elimination:  renal
• half-life of desogestrel is determined to be of 30 hours.

Drug Interactions:

• Enzyme-inducing drugs (rifampicin, rifabutine, efavirenz, nevirapine, lopinavir, ritonavir, phenobarbital, phenytoin, carbamazepine, griseofulvin, etc.) reduce the effectiveness of the contraceptive. 
• Inducers of liver enzymes can increase the metabolism of desogestrel and etonogestrel and reduce their circulating levels. This may result in contraceptive failure.
• Many antivirals for HIV/AIDS and HCV, such as boceprevir, nelfinavir, nevirapine, ritonavir, and telaprevir, may increase or decrease levels of desogestrel and etonogestrel
• CYP3A4 inhibitors including strong inhibitors like clarithromycin, itraconazole, and ketoconazole and moderate inhibitors like diltiazem, erythromycin, and fluconazole may increase levels of desogestrel and etonogestrel

Side- Effects:

• Vaginal bleeding may occur at irregular intervals
• Menstrual irregularities
• Amenorrhea
• Headaches
• Nausea
• Breast tenderness
• Mood changes (e.g., Depression)
• Weight gain
• Acne
• Hirsutism
• Symptoms of angioedema

Nursing Considerations

• Monitor fluid intake and output, and weigh patient daily.
• Evaluate patient for breast tenderness and swelling. As needed, administer analgesics and apply cool compresses.
• Do not administer to women with breast cancer, severe or recent liver disease, unexplained vaginal bleeding, active thromboembolic disorders.
• Consider collecting detailed history of all medications and history of diseases like breast cancer, thrombosis, diabetes and tuberculosis.
• In case of severe gastrointestinal disturbance, absorption may not be complete and additional contraceptive measures should be advised.

Patient/ Family Education:

• Teach the patient how to take the medicine according to the instructions and when to take the medicine.
• Teach the client regarding the possible side- effects of the medicine.
• Educate when to get medical help like:
• Possible signs of a blood clot e.g. severe pain or swelling in either of your legs; unexplained pains in the chest, breathlessness, an unusual cough, especially when you cough up blood
• Sudden, severe stomach-ache or jaundice (you may notice yellowing of the skin, the whites of the eyes, or dark urine, possibly a sign of liver problems)
• Feel a lump in your breast
• Sudden or severe pain in the lower abdomen or stomach area (possibly a sign of a pregnancy outside the womb)
• Unusual, heavy vaginal bleeding 
• Suspect that you are pregnant.​
• When pregnancy occurs during treatment with Desogestrel , further intake should be stopped.
• Teach the methods of breast self- examination.

Mechanism of Action:

Spironolactone analogue with anti-mineralocorticoid and antiandrogenic activity; suppresses luteinizing hormone and ovulation by binding to the progesterone receptor; also alters cervical mucus, causing unfavourable sperm penetration; changes to the endometrial lining may decrease implantation

Indications:

Oral Contraception

Contraindications & Cautions:

• Renal impairment
• Adrenal insufficiency
• Presence or history of cervical cancer or progestin-sensitive cancers
• Liver tumors, benign or malignant, or hepatic impairment
• Undiagnosed abnormal uterine bleeding

Metabolism and Half- Life :

• Peak plasma time: 2-6 hr; Protein bound: 95-97% (albumin)
• Extensively metabolized
• Drospirenone is also subject to oxidative metabolism catalyzed by CYP3A4
• Half-life: ~30 hr
• Excretion: Nearly complete after ~10 days; amounts excreted in feces slightly higher compared with urine

Drug Interactions:

• Inhibitors and inducers of the cytochrome P450 enzyme CYP3A4 may influence the levels and efficacy of drospirenone
• Drospirenone may interact with potassium-sparing medications such as ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, potassium supplements, heparin, Anti mineralocorticoids, and nonsteroidal anti-inflammatory drugs to further increase potassium levels. This may increase the risk of hyperkalemia (high potassium levels).
• Potential for increased serum potassium concentration if drospirenone co administered with other drugs that increase potassium levels
• Strong CYP3A4 inhibitors may result in a moderate increase of drospirenone systemic exposure

Side- Effects:

• Unscheduled bleeding, cycle 1
• Unscheduled bleeding, cycle 13
• Acne
• Metrorrhagia
• Headache
• Breast pain
• Weight increased ​
• Dysmenorrhea ​
• Nausea ​
• Vaginal hemorrhage ​
• Libido decreased​
• Breast tenderness ​
• Menstruation irregular​

Nursing Considerations

• Monitor fluid intake and output, and weigh patient daily.
• Monitor biochemical parameters of liver, thyroid, adrenal and renal function, serum levels of (carrier) proteins, e.g. corticosteroid binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis.
• Before oral contraceptives are used, a thorough history and physical examination should be performed, including a blood pressure determination and the family case history carefully noted.
• Evaluate patient for breast tenderness and swelling. As needed, administer analgesics and apply cool compresses.
• Assess for side effects like vaginal bleeding.
• Monitor serum potassium level regularly
• Carefully observe females for history of depression and discontinue drospirenone if depression recurs to a serious degree
• Consider possibility of ectopic pregnancy in women who become pregnant or report lower abdominal pain
• Discontinue if jaundice or acute or chronic disturbances of liver function develop; do not resume until LFTs return to normal and causation identified; drospirenone contraindicated with hepatic impairment or benign or malignant liver tumors.
• Progestins may decrease insulin sensitivity; patients with diabetes may be at greater risk of hyperglycemia and may require additional medication adjustments or monitoring.

Patient/ Family Education:

• Women receiving oral contraceptives (OCs) should be instructed in self-examination of their breasts. They should notify their physicians whenever any masses are detected. A yearly clinical breast examination is also recommended.
• Inform the patient that they may have light bleeding or spotting when you first take the pill.
• Advice to Take this medicine at the same time each day. Birth control pills work best when no more than 24 hours pass between doses.
• Do not skip or delay taking your pill by more than 24 hours.
• Use another form of birth control if you vomit or have diarrhea within 3 to 4 hours of using the pills
• Teach when and how to take the medicine properly and need for additional contraceptive measures when needed.
• Inform about the need for regular blood tests and possible side- effects of the medication.

Mechanism of Action:

 Progestin; inhibits secretion of gonadotropins from pituitary gland; prevents follicular maturation and ovulation, increases viscosity of cervical mucous, and stimulates growth of mammary tissues

Indications:

Contraception

Contraindications & Cautions:

• Documented hypersensitivity
• Known or suspected breast cancer, personal history of breast cancer, or other progestin-sensitive cancer, now or in the past
• Liver tumors, benign or malignant, or active liver disease
• Undiagnosed abnormal vaginal bleeding
• Hypersensitivity to etonogestrel or component of the formulation
• Current/history of thrombophlebitis, thromboembolic disorders
• Caution in family history of DVT/PE, current/history of depression, endometriosis, DM, HTN, bone mineral density changes, renal/hepatic impairment, bone metabolic disease, SLE; conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)
• Women with family history of breast cancer or who develop breast nodules should be carefully monitored

Metabolism and Half- Life:

• Onset: Inhibition of ovulation: within 1 day
• Duration: Inhibition of Ovulation: 3 years
• Absorption: Rapidly absorbed into the circulation.
• Bioavailability: approx 100%
• Time to peak plasma concentration: within 1- 13 days
• Distributions: enters breast milk. Plasma protein binding: 66% to albumin; approx 32% to sex hormone binding globulin.
• Metabolized by liver.
• Excretion via urine and faeces.
• Half-life:  approx 25- 30 Hours.

Drug Interactions:

• May decrease plasma concentration and efficacy with efavirenz, phenytoin, barbiturates, rifampicin, carbamazepine, nelfinavir, ritonavir, boceprevir.
• May increase the plasma concentration with moderate to strong CYP3A4 inhibitors (e.g., fluconazole, diltiazem, erythromycin, itraconazole, clarithromycin)
• Plasma and tissue levels of ciclosporin may be increased, while lamotrigine may be decreased.
• May increase the plasma concentration with grapefruit.

Side- Effects:

• Significant: Ovarian cyst, increased risk of breast or cervical cancer, retinal vein thrombosis, thromboembolism (e.g., DVT), other vascular events (e.g., MI, Stroke), changes in menstrual bleeding patterns, weight gain, increased risk of gall bladder disease, increased LDL concentration, sustained hypertension, Fluid retention, depressed mood, depression, chloasma.
• Rarely: ectopic pregnancy, hepatic adenomas.
• GI disorders: abdominal pain, nausea, flatulence
• General disorders and administration site conditions: implant site pain and reactions, fatigue, pain, influenza –like illness.
• Immune system disorders: Hypersensitivity reactions
• Metabolism and nutrition: increased appetite
• Musculoskeletal and connective tissue disorders: back pain
• Nervous system disorders: headache, dizziness
• Psychiatric disorders: nervousness, affect lability
• Reproductive system and breast disorders: vaginal infections, vaginitis, breast tenderness, breast pain, decreased libido, dysmenorrhoea, leucorrhoea, amenorrhoea
• Respiratory: pharyngitis
• Skin: acne, alopecia
• Vascular: hot flushes
• Potentially fatal: pulmonary embolism

Complications of Insertion

• Implant removal may be difficult or impossible if implant not inserted correctly, inserted too deeply, not palpable, encased in fibrous tissue, or has migrated
• Exploratory surgery without knowledge of exact location of implant is strongly discouraged
• Migration of implant within arm from insertion site, which may be related to deep insertion, reported; in cases where implant has migrated to pulmonary artery, chest pain and/or respiratory disorders (such as dyspnea, cough, or hemoptysis) reportred; others were asymptomatic; endovascular or surgical procedures may be needed for removal
• If at any time implant cannot be palpated, it should be localized; removal is recommended
• If inserted deeply (intramuscular or in fascia), neural or vascular injury may occur; to help reduce risk of neural or vascular injury insert product subdermally just under skin at inner side of non-dominant upper arm overlying the triceps muscle about 8-10 cm (3-4 inches) from medial epicondyle of humerus and 3-5 cm (1.25-2 inches) posterior to sulcus (groove) between biceps and triceps muscles; this location avoids large blood vessels and nerves lying within and surrounding the sulcus

Nursing Considerations

• Rule out pregnancy prior to implant insertion
• Monitor blood pressure, intake and output and weight regularly.
• Watch for signs and symptoms of thromboembolic disorders, visual changes and depression.
• Perform diagnostic measures to rule out malignancy in all cases of undiagnosed vaginal bleeding.
• Women with family history of breast cancer or who develop breast nodules should be carefully monitored
• Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist
• Discontinue 4 week before major surgery or prolonged immobilization.
• When implant broken or bent, may increase release rate of etonogestrel; when implant removed, remove it in its entirety.
• Due to the risk of thromboembolism associated with pregnancy and immediately following delivery, the drug should not be used before 21 days postpartum; women with a history of thromboembolic disorders should be made aware of the possibility of recurrence
• The implant should be removed if blood pressure rises significantly and becomes uncontrolled

Patient/ Family Teaching:

• Educate the patient regarding the use of implant before starting the therapy. Explain in detail the uses and complications that may arise due the device.
• Explain the possible side- effects and when to get the medical help.
• Advise for regular blood pressure and glucose checkups. The implant should be removed if blood pressure rises significantly and becomes uncontrolled
• Do not drive, use machinery, or do anything that needs alertness until you can do it safely.
• Limit alcoholic beverages.
• This medication may cause blotchy, dark areas on your face and skin (melasma). Sunlight may worsen this effect. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.
• Be sure to have regular breast exams and gynaecology check-ups. You will also need to do breast self-exams as you have been told.
• After etonogestrel has been put in, use a non-hormone birth control like condoms until the placement of etonogestrel has been checked.
• If you cannot feel the implant or if you think that the implant has broken or bent while in your arm, talk with the doctor.
• Problems may happen when etonogestrel is put in or taken out. These include pain; burning, numbness, or tingling; bruising or bleeding; scars; or infection.
• If you get pregnant while taking etonogestrel, the chance of pregnancy outside of the uterus (ectopic pregnancy) may be raised
• The rod must be removed after 3 years and can be replaced if continued birth control is desired. The rod can be removed at any time by a trained health care professional if birth control is no longer desired or if there are side effects.
• Re-start contraception immediately after removal of the implant if continued contraceptive protection is desired

Mechanism of Action:

Inhibits secretion of pituitary gonadotropins. Therapeutic Effect: Prevents follicular maturation, ovulation. Causes endometrial thinning.

Indications:

PO:

• Reduction of endometrial hyperplasia in non-hysterectomized postmenopausal women (concurrently given with estrogen to women with intact uterus)
• Treatment of secondary amenorrhea
• Abnormal uterine bleeding due to hormonal imbalance.

IM:

• Adjunctive therapy
• Palliative treatment of inoperable, recurrent, metastatic endometrial carcinoma
• Prevention of pregnancy
• Endometriosis associated pain.

OFF-LABEL: Treatment of paraphilia/hypersexuality.

Contraindications & cautions:

• Hypersensitivity to medroxyprogesterone.
• Breast cancer (known, suspected or prior history)
• History of or active thrombotic disorders (thrombophlebitis, thromboembolic disorders)
• Known or suspected pregnancy
• Severe hepatic impairment
• Undiagnosed abnormal vaginal bleeding
• Cerebrovascular disease.

Cautions:

Pts with conditions aggravated by fluid retention (asthma, seizures, migraine, cardiac/renal dysfunction), diabetes, history of mental depression, preexisting hypercholesterolemia, hypertriglyceridemia

Metabolism and Half- Life:

• Well, absorbed after PO administration. Slowly absorbed after IM administration.
• Protein binding: 90%. Metabolized in liver.
• Primarily excreted in urine.
• Halflife: PO: 12–17 hrs. IM: 40–50 days

Drug Interactions:

• Strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) may decrease effects.
• St. John’s wort may decrease effect of progestin contraceptive.
• Herbals with progestogenic properties (e.g., bloodroot, chasteberry, yucca) may increase adverse effects.
• May alter serum thyroid, LFT, PT, HDL, total cholesterol, triglycerides, meta- pyrone test.
• May increase LDL.

Side- Effects:

Frequent:

Transient menstrual abnormalities (spotting, change in menstrual flow/ cervical secretions, amenorrhea) at initiation

of therapy.

Occasional:

 Edema, weight change, breast tenderness, anxiety, insomnia, fatigue, dizziness.

Rare:

Alopecia, depression, dermatologic changes, headache, fever, nausea.

Nursing Considerations

Baseline assessment

• Obtain usual menstrual history.
• Question for hypersensitivity to progestins, possibility of pregnancy before initiating therapy.
• Obtain baseline weight, serum glucose, B/P.

Intervention/evaluation

• Check weight daily; report weekly gain of 5 lb or more.
• Assess B/P periodically.
• Assess skin for rash, urticaria.
• Report development of chest pain, sudden shortness of breath, sudden decrease in vision, migraine headache, pain (esp. With swelling, warmth, redness) in calves, numbness of arm/leg (thrombotic disorders) immediately.
• Monitor patient for fluid retention and for signs and symptoms of thrombophlebitis, including pain, swelling, and redness of lower legs.
• Assess for visual disturbances and headache. If ocular exam shows papilledema or retinal vascular lesions, drug should be discontinued.
• Evaluate liver function tests.
• Watch for abdominal pain, fever, malaise, jaundice, darkened urine, and clay-coloured stools

Patient/family teaching

• Report sudden loss of vision, severe headache, chest pain, coughing up of blood (hemoptysis), numbness in arm/ leg, severe pain/swelling in calf, unusually heavy vaginal bleeding, severe abdominal pain/tenderness.
• Depo- Provera Contraceptive injection should be used as long-term birth control method (e.g., longer than 2 yrs) only if other birth control methods are inadequate.
• Advise patient that drug may cause nausea, vomiting, headache, abdominal pain, painful breast swelling, and abnormal bleeding pattern. Instruct her to report these effects if pronounced.
• Tell patient to promptly report bloating, swelling, appetite loss, rash, yellowed skin, mood changes or depression, nervousness, dizziness, chest pain, shortness of breath, visual disturbances, or severe headache.
• Teach patient how to perform breast self-exams.
• Tell patient she must undergo yearly physical examinations with Pap smear.

Mechanism of Action:

• Local mechanism by which continuously released LNG enhances contraceptive effectiveness has not been demonstrated. Suggested mechanisms of preventing pregnancy are thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium.
• Synthetic progestin, ovulation is inhibited from a negative feedback mechanism on hypothalamus, leading to reduced secretion of FSH and LH.

Indications:

• Intrauterine contraception for up to 5 years
• Heavy menstrual bleeding for women who choose to use intrauterine contraception
• Emergency contraception to prevent pregnancy.

Contraindications & Cautions:

Mirena—

• Hypersensitivity to drug or its components
• Known or suspected pregnancy
• Congenital or acquired uterine anomaly
• Acute pelvic inflammatory disease (PID) or history of PID (unless patient had subsequent intrauterine pregnancy)
• Postpartum endometritis or infected abortion within past 3 months
• Known or suspected uterine or cervical neoplasia or unresolved abnormal Papanicolaou (Pap) test
• Untreated acute cervicitis or vaginitis
• Acute hepatic disease or hepatic tumor (benign or malignant)
• Genital bleeding of unknown cause
• Conditions associated with increased risk of infection
• Genital actinomycosis
• Previously inserted intrauterine device that has not been removed
• Known or suspected breast cancer
• History of ectopic pregnancy or conditions that predispose to it

Plan B —

• Hypersensitivity to drug or its components
• Known or suspected pregnancy
• Undiagnosed abnormal genital bleeding

Metabolism and Half- Life:

Absorption: LNG concentrations

• Kyleena
  • 12 months: 199 pg/mL
  • 24 months: 120 pg/mL
  • 36 months: 122 pg/mL
  • 48 months: 79 pg/mL
  • 60 months: 65 pg/mL

• Liletta
  • 6 months: 195 pg/mL
  • 12 months: 168 pg/mL
  • 24 months: 150 pg/mL
  • 36 months: 132 pg/mL
  • 48 months: 114 pg/mL
  • 60 months: 101 pg/mL
  • 72 months: 93 pg/mL

• Mirena
  • 12 months: 150 pg/mL
  • 24 months: 192 pg/mL
  • 60 months: 159 pg/mL
  • 72 months: 121 pg/mL

• Skyla
  • 12 months: 7 pg/mL
  • 24 months: 62 pg/mL

Metabolism

• LNG conjugates to form sulfate conjugates and, to a lesser extent, glucuronide conjugates in serum
• Also, studies demonstrated oxidative metabolism of LNG catalyzed by CYP enzymes, especially CYP3A4

Elimination

Clearance

•Skyla and Kyleena: 1 mL/min/kg

Half-life

• Mirena: ~17 hr
• Skyla: ~ 20 hr
• Liletta: ~13.9 hr
• Kyleena: ~20 hr

Excretion

All formulations: ~45% (urine); ~32% (feces)

Tablet:

• Absorption: Peak Plasma Time: 1.4-2.5 hr
• Distribution: Protein Bound: 50%
• Metabolism: Metabolized in liver
• Metabolites: Tetrahydrolevonorgestrels, hydroxynorgestrel, conjugates of sulfate or glucuronide
• Elimination: Half-Life: 11-45 hr
• Excretion: Urine (40-50%), feces (32%)

Drug interactions

• Hepatic enzyme-inducing drugs (such as barbiturates, carbamazepine, phenytoin, rifampin): decreased Plan B efficacy
• Glucose: altered level (Mirena)

Side – Effects:

• CNS: headache (Mirena, Plan B), fatigue, dizziness (Plan B), severe headache, migraine, nervousness, depression (Mirena)
• CV: hypertension (Mirena)
• EENT: sinusitis (Mirena)
• GI: nausea, vomiting, abdominal pain (Mirena, Plan B), diarrhea (Plan B), intestinal perforation or obstruction (Mirena)
• GU: breast tenderness (Mirena, Plan B); lighter or heavier menstrual bleeding (Plan B); breast pain; increased progesterone levels; ovarian cysts; dysmenorrhea; amenorrhea; spotting; erratic or prolonged menstrual bleeding; pelvic infection; vaginitis; cervicitis; dyspareunia; leukorrhea; decreased libido; abnormal Pap smear; expulsion, embedment in myometrium, adhesions, cervical or ureteral perforation (Mirena)
• Hematologic: anemia (Mirena)
• Hepatic: jaundice (Mirena)
• Musculoskeletal: back pain (Mirena)
• Respiratory: upper respiratory tract
• Infection (Mirena)
• Skin: skin disorder, acne, eczema, hair loss (Mirena)
• Other: water retention, weight gain, sepsis (Mirena)

Nursing Considerations

Patient monitoring

• Monitor blood pressure.
• Watch for adverse reactions, especially changes in menstrual bleeding.
• Monitor blood glucose level in diabetic patients.
• Check liver function tests frequently

Patient teaching

• Tell patient taking either product that drug does not prevent HIV or other sexually transmitted diseases.
• Teach patient using Mirena how to check (after menstrual period) to make sure thread still protrudes from cervix. Caution her not to pull on thread, because this could cause displacement.
• Instruct patient using Mirena to immediately report fever, chills, unusual vaginal discharge, or abdominal or pelvic pain or tenderness.
• Explain that for maximum efficacy, patient should take Plan B as soon as possible after unprotected sex.
• Inform patient that Plan B isn’t intended for routine contraception and doesn’t terminate existing pregnancy.
• Tell patient to report adverse reactions.

Mechanism of Action:

Progestin-only oral contraceptives prevent conception by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, lowering the mid-cycle luteinizing hormone and follicle-stimulating hormone peaks, slowing the movement of the ovum through the fallopian tubes, and altering the endometrium

Indications:

Contraception

Contraindications & Cautions:

• Known or suspected pregnancy
• Known or suspected breast cancer
• Undiagnosed abnormal genital bleeding
• Hypersensitivity to norgestrel or excipients
• Benign or malignant liver tumors
• Acute liver disease

Metabolism and Half- Life:

Serum progestin levels peak about two hours after oral administration, followed by rapid distribution and elimination. By 24 hours after drug ingestion, serum levels are near baseline, making efficacy dependent upon rigid adherence to the dosing schedule. There are large variations in serum levels among individual users. Progestin-only administration results in lower steady-state progestin levels and a shorter elimination half-life than concomitant administration with estrogens.

Drug Interactions:

• Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects
• Strong CYP3A4 inducers: Contraceptive failure is possible owing to decreased serum concentration of norgestrel
• Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods
• Sex hormone-binding globulin concentrations may be decreased
• Thyroxine concentrations may be decreased, owing to a decrease in thyroid-binding globulin

Side- Effects:

• Irregular bleeding
• Dizziness
• Nausea
• Increased appetite
• Abdominal pain
• Cramps or bloating
• Breast tenderness or discharge
• Pain in the abdomen, chest, groin or leg
• Severe headache

Nursing Considerations

Monitoring:

• Yellowing of skin or eyes, especially with fever, tiredness, loss of appetite or dark-colored urine
• Vaginal bleeding with sex
• Menstrual periods that last more than 8 days or are unusually heavy
• Worsening migraines or migraines with vision changes
• Missed periods, tender breasts, nausea, fatigue, and/or needing to urinate more urgently or frequently

Patient advice:

• Advise patient to start taking this drug the day after they switch from another oral contraceptive, vaginal ring, or patch.
• The patient must use a condom or barrier method during sex for the first 2 days after starting to take this drug.
• If the patient is less than 3 hours late, they are to take the tablet immediately and resume their regular scheduled hour the next day.
• If the patient is more than 3 hours late, they are to take the tablet as soon as they remember and resume their regular scheduled hour the next day. This may result in 2 tablets in a 24-hour window.
• Advise the patient to use a condom or another barrier form of contraception every time they have sex during the 48 hours after restarting this drug.
• A pregnancy test should be taken or talk to the medical provider if patient’s period is late after missing any doses within the last month.
• If the patient has taken an emergency contraceptive within the last 5 days, advise the patient to start taking this drug after 5 days have passed. The patient must also use a condom or barrier during sex until the next period.​
• If the patient develops lower abdominal pain mostly on one side, advise to seek medical help immediately.​
• If the patient’s period is late after missing any tablets in the last month, has not had a period for 2 months, or if pregnancy is suspected, advise the patient to take a pregnancy test or talk with their healthcare provider.​
• Advise the patient to continue to take this drug if migraines worsen or new migraines with auras develop and talk to their healthcare provider.​
• Advise patient to seek medical help immediately if they develop symptoms of yellowing of the whites of the eyes or skin.​
• If the patient repeatedly has vaginal bleeding that is brought on by sex, advise the patient to continue taking this drug and talk to their healthcare provider.​
• If the patient’s periods are unusually heavy or last more than 8 days, advise the patient to continue taking this drug and talk to their healthcare provider​

Mechanism of Action:

Suppresses ovulation by altering the vaginal epithelium, relaxing uterine smooth muscle, and promoting mammary tissue growth. Also inhibits pituitary activity and causes withdrawal bleeding in presence of estrogen.

Indications:

• Secondary amenorrhea
• Dysfunctional uterine bleeding
• To prevent postmenopausal estrogen- induced endometrial hyperplasia
• Corpus luteum insufficiency
• Assisted reproduction technology
• Fetal Maturation
• Progesterone Insufficiency
• Female Infertility

Contraindications & Cautions:

• Hypersensitivity to drug, peanuts (injection, micronized capsules), or sesame (injection)
• Thromboembolic disease
• Cerebrovascular disease
• Severe hepatic disease
• Porphyria
• Breast or reproductive system cancer
• Missed abortion
• Undiagnosed vaginal bleeding
• Diagnosis of pregnancy

Use cautiously in:

• Renal or cardiovascular disease, seizure disorders, fluid retention, diabetes mellitus, asthma, migraine, depression
• History of hepatic disease
• Breastfeeding patients

Metabolism and Half- Life:

Progesterone micronized

• Half-Life: 5 min
• Peak serum time: 3 hr; Protein Bound: 96-99%
• Metabolism: Liver to metabolites
• Enzyme induced: CYP3A3/4
• Excretion: Urine (50-60%); feces, including bile (10%)

Progesterone intravaginal gel

• Half-Life: 5-20 min
• Excretion: Urine (50-60%); feces, including bile (10%)
• Protein bound: 96-99%
• Peak serum time: 8 hr
• Metabolism: Primarily by hepatic CYP3A3/4

Drug Interactions:

• Conjugated estrogens: increased levels of both drugs
• Alkaline phosphatase, amino acids, low-density lipoproteins: increased levels
• Chloride and sodium excretion: reduced (with high doses)
• High-density lipoproteins: decreased level
• Pregnanediol excretion: reduced
• Thyroid function tests: altered results
• Red clover: interference with drug effects
• Smoking: increased risk of thromboembolic effects

Side- Effects:

• CNS: depression, emotional lability, cerebrovascular accident
• CV: thrombophlebitis, thromboembolism
• EENT: retinal thrombosis
• GI: abdominal cramps
• GU: amenorrhea, breakthrough bleeding, spotting, cervical erosions, breast tenderness, menstrual flow changes, galactorrhea
• Hepatic: hepatitis
• Respiratory: pulmonary embolism
• Skin: melasma, rash, angioedema
• Other: gingival bleeding, weight gain or loss, hypersensitivity reactions including anaphylaxis

Nursing Considerations

Patient monitoring:

• Watch for evidence of thromboembolic disorders, including cerebrovascular accident, pulmonary embolism, diplopia, proptosis, or sudden partial or complete vision loss (may signal retinal thrombosis). If these occur, discontinue drug and notify prescriber immediately.
• Assess for emotional lability and Depression.

Patient teaching

• Teach patient to recognize and immediately report signs and symptoms of thromboembolic disorders.
• Instruct patient and significant other to stay alert for and immediately report depression.
• Advise patient to monitor weight regularly and report significant changes.
• Tell female patient that drug may cause menstrual abnormalities.
• Advise female patient to discuss breastfeeding with prescriber before taking drug.
• Instruct patient to immediately report possible pregnancy.
• Tell patient that smoking increases thromboembolism risk. Encourage her to stop smoking if she smokes.

REFERENCES

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