Progesterone ( *** ) @ - Bleeding disorders
Drug Name:Progesterone ( *** ) @ - Bleeding disorders
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Other Information
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Ammenorhoea, functional uterine bleeding
Interacting drugs- summary
Contraceptives oral +
Acetoaminophen
onset of acetoaminophens effect delayed or decreased
slightly, but the ultimate effect dose not to be significantly
different
Anticoagulants
since OCs increase levels of certain circulating clotting factors
and reduce antithrombin III levels, therapeutic efficacy of the
anticoagulants decreased by OCs. However, both an
increased and decreased effect has occurred
Antidepressants tricylic,/ Benzodiazepines / betablockers/ Caffeine / Corticosteroids /
Theophylline
the hepatic metabolism of these agents decreased by OCs
resulting in increased therapeutic effects on toxicity.
Benzodiazepines
OCs increase the clearance of the benzodiazepines that
undergo glucoronidation ( lorazepam, oxazepam, termazepam )
due to increased metabolism
Clofibrate
OCs increase the elimination of clofibric acid, the active form
of clofibrate
Salicylates
OCs increase the metabolic clearance of salicylates,
decreasing the therapeutic effects.
Antibiotics +Oral Contraceptive
Coadmin. of grisefluvin, penicillins or tertracycline with OCs
decrease the pharmacologic effects of OCs. due to altered
gut metabolism secondary to changes in intestinal flora.
menstrual irregularties ( spotting, breakthrough bleeding ) and
pregnancy may occur. An alternate or additional form of birth control
advisable
Barbiturates / Hydantoins/ Rifampicin + Contraceptives
these agents increase the hepatic metabolism of the OCs via
hepatic microsomal enzyme induction, resulting in decreased
effectiveness of the OCs., menstrual irregularities ( spotting, break thru
bleeding and pregnancy occur. An alternate form
of birth control advisable during concomittant use.
Indication:
Ammenorhoea, functional uterine bleeding
Adverse Reaction:
Serious- thrombophlebitis, and venous thrombosis, with or without embolism, pulmonary embolism, coronary thrombosis, MI, cerebral thrombosis, arterial thromboembolism, cerebral haemorrhage, hypertension, gall bladder disease, congenital abnormalities, hepatic adenomas or benign liver tumors, hepatocellular carconoma, mesenteric thrombosis,
Budd-Chiari syndrome
GU- breakthrough bleeding, (majority > 80% resolve in 3 months) spotting, chnage in menstrula flow, amenorrhea during and after treatment, change in cervical secretions, invasive cervical cancer, vaginal candidiasis
Breast chnges- tenderness, enlargement, secretion, diminution in lactation when given immediately postpartum.
GI- nausea and vomitiing(occuring in 10% of patients during the first cycle, less common with low doses, and majority resolve in 3 months) abdominal cramps, bloating, cholestatic jaundice
Dermatologic- melasma, rash(allergic)
CNS- migraine., mental depression
Opthalmic- changes in comeal curvature (sleepening) contactvlens intolerance, neuro-ocular lesions (eg. retinal thrombosis, optic neuritis)
Miscellaneous- edema, weight change(increase or decrease) reduced carbohydrate tolerance,prevalence of cervical chalmydia may be increased
Contra-Indications:
Pregnancy, lactation, thromboembolism. Undiagnosed vaginal bleeding,liver diseases,
hormone dependent carcinoma.missed incomplete aborption.
Special precaution:
CVS disease, hypotension, mental depression, renal disease, diabetes, asthma, epilepsy,
migraine.
Monitoring- take a complete medical and family history to initiation of therapy. Physical examination before initiation of OCs who are being treated for lipidemias. Some progestins may elevate LDL levels and decrease HDL levels making hyperliperidemia control more difficult. Consider witholding the OC if the dyslipidemia does not respond (ie LDL of 190)
Uterine fibroids- preexisting uterine leiomymate (uterine fibroids) may increase in size. However there is no evidence of this with low dose OCs. In addition, data from Great Britan indicates that the risk of developing uterine fibroids is actually reduced with OC use.
Depression- the incidence of depression in OC users ranges from < 5% to 30%. Pyridoxine deficiency may be a factor in the depression. Pyridocine 25 to 50mg per day has been recommended. Patients becoming significantly depressed
should discontinue medication to determine if symptom is drug-related.
Pyridoxine deficiency- OC users may have relative pyridoxine deficiency ,clinical significance is unknown.
Fluid retention- OC may cause fluid retention, prescribe with caution and monitor patients with conditions which might be aggravated by fliud retention (eg. convulsive disorders, migraine syndrome, asthma, cardiac , hepatic or renal dysfunction)
Hepatic function- patients with a history of jaundice during pregnancy have an increased risk of recurrence of jaundice, if jaundice occurs, discontinue use.
Contact lens wearers- who develop changes in vision oe l;ens tolerance should be assesed by an opthalmologist.
Consider temporary or permanent cesation of wear.
Serum folate levels- may be depresed by therapy.Folic acid supplements are recommended.
Acute intermittant porphyria- estrogens have been reported to precipitate attacks of acute intermittant porphyria.
Use with caution in susceptible patients.
Vomiting/diarrhea- several cases of OC failure have been reported in assocition with vomiting and diarhea. If significant GI distuerbances occurs, a back-up method of contraception for the remainder of the cycle is recommended.
Sexually transmitted disease- STDs-advice patients that OC s do not protect against infectionnand other STDs.
Photosensitivity- photosentrization may occur., therfore caution patients to take protective measures against exposure to ultraviolet or sunlight.
Warnings-
Cigreete smoking- increases the risk of cardiovascular side efects from OCs. Women whom use OCs should not smoke.
Risks of OC use- risk of morbidity/mortality increases significantly in the presence of other underlying risk factors such as hypertension,hyperlipidemias ,obesity and diabetes.
Thromboembolic and cardiovascular problems- be alert to theearliest symptoms of thromboembolic and thrombotic disorders. Should any of these occur or be suspected discontinue the drug immediately.
Myocardial infarction- MI- risk associated with OC use is increased. The risk is very low in women , 30 years. It is estimated that the relative risk of heart attack for current OC users is 2 to 6.
Long term use- data suggest that the increased risk of MI persists after discontinuation of long-term use, the highest risk group includes women 40 to 49 years who used OC for> 5 years.
Smoking- OC users who also smoke have a fivefold increased risk of fatal infarction compared to non-smoking users.but a 10 to 12 fold increased risk compared to nonusers who do not smoke.
Cerbral vascular disease- OCs increase the risks of cerebrovascular events (thrombotic and hemorrhagic stroke) although in general the risk is greatest in hypertensive women > 35 years of age who also smoke.
Vascular disease- a positive association is observed between the amount of estrogen and progestin in OCs and the risk of vasculardisease
Age- the risk of cerebrovascuar and circulatory disease in OC users is substantially increased in women > 35 years of age with other risk factors eg. smoking, uncontrolled hypetension, hypercholesterolemia (LDL 190) , obesity, diabetes. cvurent clinical practice invloves the use of lower-ostrogen doseformulations combined with careful restriction of OC use to women who do not have the various risk factors.
Post surgical thromboembolism- risk isincreased 2 to 4 fold. If possible, discontinue OCs at least 2 to 4 weeks before and 2 weeks after surgery as OCs recassociated with an increased risk of thromboembolism.
Subarachoid hemorhage- has been increased by OC use.Smoking alone increases the incidence of these accidents, smoking and OC use appear to work togeter to produce combined risk greater than either or alone.
Persistence risk- an increased risk may persist for at least 6 years after discontinuation of OC use for cerebrovascular disease and at least for MI in users 49 years of age whohad used OCs for > 5 years.
This risk was not demonstrated in other age groups.
Ocular lesions-discontinue medication if there is unexplained loss of vision, onset of proptosis, or diplopia, papilledema or retinal vascular lesions.
Carcinoma- studies have reported an increased risk of endometrial carcinoma associated with the prolonged use of estrogen in postmenopausal women. However, the risk appears to be decreased in OC users due to progestin component.
Hepatic lesion- while hepatic adenoma is uncommon consider it in women presenting abdominal pain and tenderness abdominal mass or shock. A few cases of hepatocellular carcinoma have been reported in women taking OCs long term.
Pregnany test- do not administer progestin-only products or progestin-estrogen combination to induce
withdrawal of bleeding as a test for pregnancy
Carbohydrate metabolism- observe prediabetic and diabetic patients receiving OCs. In recent study OC users are less likely to develop diabetes than nonusers.
Lipid profile- triglycerides may increase some progestins decrease HDL while some estrogens increase HDL.
Because the net result of OC depends on a balance acheived between doses of the agents, consider this when choosing a product.
Elevated blood pressure- and hypertension may occur within a few months of beginning use. Discontinue the use if elevated blood pressure occurs.
Headaches- onset or exacerbation of migraine or development of headache of a new pattern which is recurrent, persistent or severe requires OC disconinuation.
Bleeding irregularities- breakthroiough bleeding (BTB) spotting,amenorhea, are requent reasons for discontinuing OCs. changing to an OC with a higher estrogen content may minimise menstrual irregularity, consider the incressed risk of thromboembolic disease.
Risks of use immediately preceding pregnancy- some extensive epidemological studies have revealed no increased risk of birth defects in OC uses prior to pregnancy.
Menopause- treatment with OCs mask the onset of the climacteric.
Fertility impairment- may occur in women discontinuing OCs.however impairment diminshes with time.
Pregnancy- rule out pregnancy before initiating or continuing the OCs, and always consider it if withdrawal bleeding dose not occur.
Lactation- if possible defer use until the infant has been weaned , however in some situations,breastfeeding is the real alternative
Dosages/ Overdosage Etc:
Indications:
Ammenorhoea, functional uterine bleeding
Dosage:
For IM use only.
5 to 10mg daily for 6 to 8 consecutive days.
Overdosage- Oral contrcaeptives
Serious ill effects have been reported following acute ovedosage of OCs in young children.
Overdosage may cause nausea. Wirthdrawal bleeding may occur in females.
Missed dose-
1. Follow your doctors orders or the directions on the label. If you miss a dose of this medicine the following information
gives some of the ways to handle missedcdose.
For monphasic, biphasic or triphasic cycles-
A. If you miss the first tablet of a new cycle-
1. Take the missed tablet as soon as you remember and take the next tablet at the usual time.
2. You may take 2 tablets in one day.
3. Then continue the regulaar dosing schedule.
4. Also, use another birth control method until you have taken seven days of your tablets after the last missed dose.
B. If you miss 1 tablet during the cycle -
1. Take the missed tablet as soon as you remember and take the next tablet at the usual time.
2. Take the next tablet at the usual time.
3. You may take 2 tablets in one day.
4. Then continue the regulaar dosing schedule.
C. If you miss 2 tablet in a row in the first or second week-
1. Take 2 tablets on the day that you remember and 2 tablets the next day
2. Continue taking 1 tablet a day
3. Also use another birth control method until you begin a new cycle.
D. If you miss 2 tablets in a row in the third week- or
If you miss 3 or more tablets in a row at any time during the cycle-
1. Using a Day 1- start : Throw out your current cycle and beginalking a new cycle.
2. Also useother birth control method until you have taken seven days of your tablets after the last missed dose.
3. You may not have a menstrual period this month.
4. But if you miss two menstrual periods ina row, call your healthcare professional.
1.Using a Sunday start- Keep taking one tablet a day from your current pack until Sunday.
2. Then, on Sunday, throw out your old pack and begin a new pack.
3. Also, use another birth control method until you havetaken seven days of your tablets after the last missd dose.
4. You may not have a menstrual period this month.
5. But if you miss two menstrual periods in a row, call your healthcare professional.
E 1.If you miss any of the last seven (inactive ) tablets of a twenty-eight-day cycle, there is nodanger ofpregnancy
2.However, the first tablet (active) of the next months cycle must be taken on the regularly scheduled day, in spite of
any missed doses, if pregnancy is to be avoided.
3. The active and inactive tablets are colored differently for your convenience
Other Information:
Sexual dysfunction- Decreased libido-
Drugs causing adverse reactions-
1. Oral contraceptives
2. Sedatives
3. Major tranqulizers
4. Lithium
5. Methyldopa
6. Clonidine
Thromboembolism- ( 1056 )
Thromboembolism is the dreaded complication in patients with atrial fibrillation or less commonly with atrial flutter ,
paticularly when the dysrhymia is chronic and when atrial stenosis is absent.
Drugs causing thromboemboilsm- ( 386 )
1. Oral contraceptives
Stroke- ( 1911 )
Embolic stroke and strokes with ruptured aneurysm characterstically beginn sudenly with the defecit reaching its maximum almost immediately. Thrombolic strokes frequently begin in a similar fashion, but may develop over a period
of several days usually progressing in a stepwise fashion ie. in a series of suden changes ratherr than smoothly.
Drugs causing adverse reactions- ( 388 )
1. Oral contraceptives
Corneal edema
Drugs causing adverse reactions- ( 388 )
1. Oral contraceptives
Patient Information:
1. Refer to patient package insert
2.To acheive maximum contraceptive effectiveness, take OCs exactly as directed at intervals not exceeding 24 hours. preferably at the same time each day.
3 Take tablets regularly with a meal or at bed time. Efficacy depends on strict adherence to the dosage schedule.
4. For missed doses- While there is likelihood of ovulation ocuring if only 1 tablet is missed, the possibility of spotting or bleeding is increased.
5. The possibility of ovulation ocuring increase with each successive day that scheduled tablets are missed. This is particularly likely to occur if > 2 consecutive tablets are missed
6. Anytime >1 active tablet have been missed,use another method of contraception for the balance of the cycle until tablets have been taken for 7 consecutive days
7. May cause spotting or breakthrough bleeding during the first few months of the therapy- if bleeding occurs in > 1 cycle or lasts more than a few days, notify physician
8. Use an additional method of birth control until the first week of administration in the initial cycle, or for the entire cycle if vomiting or diarrhea occurs.
9. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to progestins. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.
10.Pregnancy - low doses og progestins such as those dose for contraception have not caused major problems when used accidentally during pregnancy,but small (low birth weight ) babies have occured in some cases.
11.Breast feeding- be sure that you have discussed the risks and benefits of the medicine with your doctor.
12. Children - no specific information available. However, this medicine is not expected to cause different side effects or problems than it does in adults.
13.Elderly- not expected to cause different side effects or problems in older people than in younger adults.
14. Other medicines -
Aminoglutethimides or
Carbamazepines or
Phenobarbital or
Phenytoin or
Rifabutin or
Rifampicin - these medicines may decrease the efects of progestins and increase the chance of
pregnancy, so use of a second form of birth control is recommended
15. Other medical problems -
Tell your doctor if you have any other medical problems especially -
Asthma - possible allergic reaction
Epilepsy or
Heart or circulation problems or
Kidney disease or
Migraine headaches - progstins may cause fluid build up and may cause these conditions to
become worse
Bleeding problems - may make diagnosis of these problems difficult
Blood clots or
Stroke or
Varicose veins - may have greater chance of causing blood clots if these conditions are already
present when high doses of progestin are taken
Breast disease - may make the conditions worse
CNS disorders- or
High blood cholesterol - effects of progestins may make these conditions worse
Dibetes mellitus - may cause an increase in blood sugar and a change in the amount of medicine required
Liver disease- may make the condition worse
Other conditions that increase the chances of osteoporosis- since it is possible that certain doses of progestins may cause temporary thinning of the bones by changing the hormone balance. It is important that your doctor know that you have an increased risk to osteoporosis. Progestins can help protect against osteoporosis in post menopausal women.
16. Missed dose -
If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.
17. Storage -
Keep out of reach of children. Store away from heat or direct sunlight. Do not store
the capsule in bathroom, near the kitchen sink, or in other damp places.
18. Outdated medicines -
Do not keep outdated medicine or medicine no longer needed. Be sure that any
discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Ref- Drug Facts And comparisons(2010)
Pharmacology:
Progestrone is secreted during the second half of the menstrual cycle and pregnancy.
The secretion increases several hundred fold during the later part of pregnancy and causes development of secretory endometrium.
Pharmacokinetics:
Progestrone absorption has been shown to be affected by particle size and vehicle used for delivery. Progestrone binds to proteins to about 95- 96%. It is metabolised mainly in the liver and the metabolites are excreted mainly in the urine. The elimination half-life of progesterone is 1- to 95 minutes.
Multiple dose of Pharmacokinetics of Progesterone Gel
Parameter Twice daily dosing for 12 days Once daily dosing for 12 days
Cmax(ng/ml) 14.57 15.97
C avg(ng/ml) 11.6 8.99
Tmax (hr) 3.55 5.4
AUC (ng*hr/ml) 138.72 391.98
T 1/2(hr) 25.91 45
Mean Single dose Relative Bioavailability of Progesterone Gel Vs IM
Parameter 8% gel 90 mg IM
Cmax (ng/ml) 14.87 53.76
C avg 0.24 (ng/ml) 6.98 28.98
AUC 0-96((ng*hr/ml) 296.78 1378.91
Tmax (hr) 6.8 9.2
T1/2(hr) 34.8 19.6
Pregnancy and lactation:
Pregnancy-
Rule out pregnancy before initiating or continuing the OCs, and always consider it if withdrawal bleeding dose not occur. Medicine during second and third trimester of pregnancy can favour the appearance of a severe cholestatis or hepatitis.
Lactation-
If possible defer use until the infant has been weaned , however in some situations, breastfeeding is the real alternative Effect of progesterone on the nursing infant has not been determined
