Proclim

Proclim contains Medroxyprogesterone, a derivative of progesterone, as its active ingredient. Proclim is active by the parenteral and oral routes of administration. It is a white to off-white, odorless crystalline powder that is stable in air and that melts between 200°C and 210°C. It is freely soluble in chloroform, soluble in acetone and dioxane, sparingly soluble in alcohol and methanol, slightly soluble in ether and insoluble in water.

Proclim is pregn-4-ene-3,20-dione,17-(acetyloxy)-6-methyl-,(6α).

depo-subQ Proclim (Proclim) 104 is indicated for the prevention of pregnancy in women of child bearing potential.

depo-subQ Proclim (Proclim) 104 also is indicated for management of endometriosis-associated pain.

In considering use for either indication, the loss of bone mineral density (BMD) in women of all ages and the impact on peak bone mass in adolescents should be considered, along with the decrease in BMD that occurs during pregnancy and/or lactation, in the risk/benefit assessment for women who use depo-subQ Proclim 104 long-term.

Contraception Studies

In three clinical studies, no pregnancies were detected among 2,042 women using deposubQ Proclim 104 for up to 1 year. The Pearl Index pregnancy rate in women who were less than 36 years old at baseline, based on cycles in which they used no other contraceptive methods, was 0 pregnancies per 100 women-years of use (upper 95% confidence interval = 0.25).

Pregnancy rates for various contraceptive methods are typically reported for only the first year of use and are shown in Table 2.

Table 2 : Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year: United States

Favorable Response = reduction in severity of symptom or sign of ≥ 1 point on a scale of 0 to 3, as compared to baseline

Additionally, scores from each of the five categories were combined, with the total (composite score) considered a global measurement of overall disease improvement. For subjects with baseline scores for each of the 5 categories, a mean decrease of 4 points relative to baseline was considered a clinically meaningful improvement. Across both studies, for both treatment groups, the mean changes in the composite score met the protocol-defined criterion for improvement.

In the clinical trials, treatment with depo-subQ Proclim (Proclim) 104 was limited to six months. Data on the persistence of benefit with longer treatment are not available.

Subjects recorded daily the occurrence and severity of hot flushes. Of the depo-subQ Proclim (Proclim) 104 users, 28.6% reported experiencing moderate or severe hot flushes at baseline, 36.2% at month 3, and 26.7% at month 6. Of the leuprolide users, 32.8% reported experiencing moderate or severe hot flushes at baseline, 74.2% at month 3, and 68.5% at month 6.

Proclim injection is used to prevent pregnancy. It is a birth control method that works by stopping a woman's egg from fully developing each month. The egg can no longer accept a sperm and fertilization is prevented.

No contraceptive method is 100 percent effective. Birth control methods such as having surgery to become sterile or not having sex are more effective than birth control pills. Discuss your options for birth control with your doctor.

Proclim does not prevent AIDS or other sexually transmitted diseases. It will not help as emergency contraception, such as after unprotected sexual contact.

Proclim injection is also used with other medicines to help relieve symptoms of inoperable, recurrent, and metastatic (cancer that has already spread) endometrial or kidney cancer.

Proclim is to be administered only by or under the immediate supervision of your doctor.

Secondary Amenorrhea

Proclim tablets may be given in dosages of 5 or 10 mg daily for 5 to 10 days. A dose for inducing an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen is 10 mg of Proclim daily for 10 days. In cases of secondary amenorrhea, therapy may be started at any time. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing Proclim therapy.

Abnormal Uterine Bleeding Due to Hormonal Imbalance in the Absence of Organic Pathology

Beginning on the calculated 16th or 21st day of the menstrual cycle, 5 or 10 mg of Proclim may be given daily for 5 to 10 days. To produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen, 10 mg of Proclim daily for 10 days beginning on the 16th day of the cycle is suggested. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing therapy with Proclim. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with Proclim.

Reduction of Endometrial Hyperplasia in Postmenopausal Women Receiving Daily 0.625 mg Conjugated Estrogens

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be re-evaluated periodically as clinically appropriate (for example, 3 to 6 month intervals) to determine if treatment is still necessary. For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

Proclim tablets may be given in dosages of 5 or 10 mg daily for 12 to 14 consecutive days per month, in postmenopausal women receiving daily 0.625 mg conjugated estrogens, either beginning on the 1st day of the cycle or the 16th day of the cycle.

Patients should be started at the lowest dose.

The lowest effective dose of Proclim has not been determined.

See also:
What is the most important information I should know about Proclim?

Known hypersensitivity to Proclim or to any other ingredients of Proclim.

Undiagnosed vaginal bleeding; known, suspected or history of breast carcinoma; previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism); active or recent (within the past year) arterial thromboembolic disease (eg, angian, myocardial infarction); known liver dysfunction or disease; missed abortion; known or suspected pregnancy.

Thrombophlebitis, thromboembolic disorders and where there is a high risk of developing such manifestations (presence or history of arterial fibrillation, valvular disorders, endocarditis, heart failure, thromboembolic ishcaemic attack, cerebral infarction; atherosclerosis; immediate post-surgery period); hypercalcaemia in patients with osseous metastases, metrorrhagia.

Progestogens are known to be porphyrogenic. Patients with history of attacks or aged <30 are at greatest risk of an acute attack while on progesterone treatment. A careful assessment of potential benefit should be made where this risk is present.

Use in pregnancy: Proclim is contraindicated in women who are pregnant. If Proclim is used during pregnancy, or if the patient becomes pregnant while using Proclim, the patient should be apprised of the potential hazard to the fetus.

Some reports suggest an association between intrauterine exposure to progestational drugs in the 1st trimester of pregnancy and genital abnormalities in male and female fetuses.

Infants from unintentional pregnancies that occur 1-2 months after injection of Proclim injectable suspension may be at an increased risk of low birth weight, which, in turn, is associated with an increased risk of neonatal death. The attributable risk is low because pregnancies while on Proclim are uncommon.

Use in lactation: Proclim and/or its metabolites are secreted in breast milk. Therefore, the use of Proclim whilst breastfeeding is not recommended.

Use Proclim injectable suspension (subcutaneous) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Proclim injectable suspension (subcutaneous). Talk to your pharmacist if you have questions about this information.
• Proclim injectable suspension (subcutaneous) is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Proclim injectable suspension (subcutaneous) at home, a health care provider will teach you how to use it. Be sure you understand how to use Proclim injectable suspension (subcutaneous). Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Proclim injectable suspension (subcutaneous) if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Be sure you know when you should begin using Proclim injectable suspension (subcutaneous) according to your doctor's instructions. Discuss any questions or concerns with your doctor.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• Proclim injectable suspension (subcutaneous) is given every 12 to 14 weeks. It is very important that you return to your doctor's office for your next injection promptly at the end of the 12 to 14 week interval. If it has been more than 14 weeks since your last dose of Proclim injectable suspension (subcutaneous), contact your doctor. You may need to have a pregnancy test before receiving another dose.
• If you miss a dose of Proclim injectable suspension (subcutaneous), contact your doctor right away.

Ask your health care provider any questions you may have about how to use Proclim injectable suspension (subcutaneous).

Use: Labeled Indications

Abnormal uterine bleeding (tablet): Treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer.

Amenorrhea, secondary (tablet): Treatment of secondary amenorrhea due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer.

Contraception (104 mg per 0.65 mL and 150 mg/mL injection): Prevention of pregnancy in females of reproductive potential.

Endometrial hyperplasia prevention (tablet): Prevention of endometrial hyperplasia in nonhysterectomized postmenopausal persons receiving daily oral conjugated estrogens 0.625 mg. Note: Due to safety considerations, when a progesterone is needed, use of micronized progesterone is preferred over Proclim (AACE [Goodman 2011]; AACE/ACE [Cobin 2017])

Endometrial carcinoma (400 mg/mL injection) (100 mg tablet [Canadian product]): Adjunctive therapy and/or palliative treatment of inoperable, recurrent, and/or metastatic endometrial carcinoma.

Endometriosis (104 mg/0.65 mL injection): Management of endometriosis-associated pain.

Off Label Uses

Abnormal uterine bleeding, acute

Data from a randomized, open-label clinical study support the use of oral Proclim in the treatment of acute uterine bleeding in nonpregnant, hemodynamically stable premenopausal women requiring emergent medical intervention. Additional data may be necessary to further define the role of Proclim in the management of this condition.

See also:
What other drugs will affect Proclim?

Aminoglutethimide administered concomitantly with DEPO-Proclim Sterile Aqueous Suspension may significantly depress the serum concentrations of Proclim. DEPO-Proclim users should be warned of the possibility of decreased efficacy with the use of this or any related drugs.

In vitro

Proclim is metabolized primarily by hydroxylation via the CYP3A4. Though no formal drug interaction trials have been conducted, concomitant administration of strong CYP3A inhibitors is expected to increase concentrations of Proclim, whereas the concomitant administration of strong CYP3A inducers is expected to decrease Proclim concentrations. Therefore, coadministration with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort) should be avoided.

Laboratory Test Interactions

The pathologist should be advised of progestin therapy when relevant specimens are submitted. The following laboratory tests may be affected by progestins including DEPOPROVERA Sterile Aqueous Suspension:

1. Plasma and urinary steroid levels are decreased (e.g. progesterone, estradiol, pregnanediol, testosterone, cortisol).
2. Gonadotropin levels are decreased.
3. Sex-hormone binding globulin concentrations are decreased.
4. Protein bound iodine and butanol extractable protein bound iodine may increase. T3 uptake values may decrease.
5. Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX, and X may increase.
6. Sulfobromophthalein and other liver function test values may be increased.
7. The effects of Proclim on lipid metabolism are inconsistent. Both increases and decreases in total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol have been observed in studies.

See also:
What are the possible side effects of Proclim?

Applies to Proclim: oral tablet

Other dosage forms:

• intramuscular injectable, intramuscular suspension

As well as its needed effects, Proclim (the active ingredient contained in Proclim) may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking Proclim, check with your doctor immediately:

Incidence not known:

• Abdominal or stomach pain
• absent, missed, or irregular menstrual periods
• anxiety
• blurred vision
• breast pain or tenderness
• changes in skin color
• chills
• clay-colored stools
• cough
• dark urine
• decrease in amount of urine
• diarrhea
• difficulty swallowing
• dizziness or lightheadedness
• eye pain
• fainting
• fast heartbeat
• fever
• headache
• hives or welts, itching, redness, swelling, or skin rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• menstrual changes
• nausea
• noisy, rattling breathing
• pain in the chest, groin, or legs, especially the calves
• pain, tenderness, or swelling of the foot or leg
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• severe, sudden headache
• shortness of breath
• slurred speech
• stopping of menstrual bleeding
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• swelling of the fingers, hands, feet, or lower legs
• troubled breathing at rest
• unexpected or excess milk flow from the breasts
• unpleasant breath odor
• unusual tiredness or weakness
• vaginal bleeding or spotting
• vision changes
• vomiting of blood
• weight gain
• yellow eyes or skin

Minor Side Effects

Some Proclim side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

Incidence not known:

• Blemishes on the skin
• discouragement
• feeling sad or empty
• hair loss, thinning of hair
• increased hair growth, especially on the face
• irritability
• lack of appetite
• loss of interest or pleasure
• nervousness
• pimples
• sleepiness or unusual drowsiness
• tiredness
• trouble concentrating
• trouble sleeping
• weight changes