Indications and dosages
➣ Symptoms of menopause, atrophic vaginitis, female hypogonadism, ovarian failure, and osteoporosis
Adults: 0.5 to 2 mg (Novular) P.O. daily continuously or cyclically. Or 1 to 5 mg (cypionate) or 10 to 20 mg (valerate) I.M. monthly. Or 50- or 100-mcg/24-hour transdermal patch applied twice weekly (Alora, Estraderm) or weekly (Climara). Or 25-mcg/24-hour patch applied q 7 days (FemPatch) or 37.5- to 100-mcg transdermal patch applied twice weekly (Vivelle). Or 2 to 4 g (0.2 to 0.4 mg) vaginal cream (Novular) applied daily for 1 to 2 weeks, then decreased to 1 to 2 g/day for 1 to 2 weeks, then a maintenance dose of 1 g one to three times weekly for 3 weeks, then off for 1 week; repeat cycle once vaginal mucosa has been restored. Or 2-mg vaginal ring q 3 months or 10-mcg vaginal tablet once daily for 2 weeks, then twice weekly.
➣ Postmenopausal breast cancer
Adults: 10 mg P.O. t.i.d. (Novular)
Adults: 1 to 2 mg P.O. t.i.d. (Novular) or 30 mg I.M. q 1 to 2 weeks (valerate)
What Abnormal Results Mean
Disorders that are associated with abnormal Novular results include:
- Early (precocious) puberty in girls
- Growth of abnormally large breasts in men (gynecomastia)
- Lack of periods in women (amenorrhea)
- Reduced function of the ovaries (ovarian hypofunction)
- Problem with genes, such as Klinefelter syndrome, Turner syndrome
- Rapid weight loss or low body fat
Q: I started on Novular about two weeks ago, and haven't had a period in about a year. I am now bleeding again. How long can I expect this to go on? It's been about 5 days now and shows no sign of stopping. I'm 54 years old.
A: While changes in your periods can be expected on Novular, patients should contact their healthcare provider right away for any unusual vaginal bleeding. This could be a sign of a serious side effect. You may also find helpful information at //www.everydayhealth.com/drugs/Novular
What should I avoid while taking Novular?
Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using this medicine.
Grapefruit and grapefruit juice may interact with Novular and lead to unwanted side effects. Avoid the use of grapefruit products.
2.2.3 GABA Receptors
Novular indirectly influences disinhibition of pyramidal cells through activation of GABA interneurons ( Rudick et al., 2003 ; Rudick and Woolley, 2003 ). Novular does not appear to alter GABA receptor kinetics globally since it does not affect GABA-evoked currents; however, Novular may act to prolong currents at a subset of GABAergic synapses ( Rudick et al., 2003 ). In particular, regulation of the α4 GABAA receptor subunit alters inhibitory postsynaptic current decay time ( Smith et al., 1998 ). Recently, immunoreactivity for the α4 and δ GABAA receptor subunits in dendrites has been shown to decrease at the proestrus/estrus cuff ( Figure 5 ) ( Sabaliauskas et al., 2010 ). These changes correlate with increases in spatial learning ( Sabaliauskas et al., 2010 ).
The sections below will provide you with more specific information and guidelines related to Novular and its correct use. Please read them carefully.
Novular was approved by the FDA in 1975 for the treatment of moderate to severe vasomotor symptoms associated with menopause as well as for the prevention of osteoporosis.
Novular tablets, the generic equivalent of Bristol Myers Squibb’s Estrace®, has been approved for marketing. Barr Pharmaceuticals’ Novular version will be available in 0.5, 1, and 2 mg strengths.
Why is this medication prescribed?
Novular is prescribed for symptomatic treatment of the usual symptoms associated with menopause (hot flushes, vaginal dryness, etc.), prevention of bone fractures associated with osteoporosis, reduction of the risk of heart attacks and strokes, and dysfunctional (excessive and painful) uterine bleeding. The vaginal cream is prescribed for vaginal or vulvar atrophy associated with menopause.
Novular enters cells freely and interacts with a cytoplasmic target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of Novular upon the target cell.
Novular binds well to both estrogen receptors, ERα and ERβ, in contrast to certain other estrogens, notably medications that preferentially act on one of these receptors. These medications are called selective estrogen receptor modulators, or SERMs.
Other uses for this medicine
This medication may also be used to regulate your menstrual cycle.
However, it is strongly advised that you talk to your doctor about the possible risks of using this drug for your particular condition.
Dosage and using this medicine
Use Novular exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.
Missed Dose of Novular
If you miss a dose of oral Novular, take it as soon as you remember.
However, if it's almost time for your next scheduled dose, skip the missed dose and continue on your regular schedule. Do not double up on doses.
If you forget a dose of Novular gel but remember more than 12 hours before your next scheduled dose, apply the missed dose immediately.
However, if you remember less than 12 hours before your next dose, skip the missed dose and continue on your regular dosing schedule.
Do not apply extra gel to make up for a missed one.
If you forget to apply Novular emulsion in the morning, apply it as soon as you remember.
Don't apply extra emulsion to make up for a missed dose.
Why the Test is Performed
In women, most Novular is released from the ovaries and adrenal glands. It is also released by the placenta during pregnancy. Novular is also produced in other body tissues, such as skin, fat, cells bone, brain, and liver. Novular plays a role in:
- Growth of the womb (uterus), fallopian tubes, and vagina
- Breast development
- Changes of the outer genitals
- Distribution of body fat
In men, a small amount of Novular is mainly released by the testes. Novular helps prevent sperm from dying too early.
This test may be ordered to check:
- How well your ovaries, placenta, or adrenal glands work
- If you have signs of an ovarian tumor
- If male or female body characteristics are not developing normally
- If your periods have stopped (levels of Novular vary, depending on the time of month)
The test may also be ordered to check if:
- Hormone therapy is working for women in menopause
- A woman is responding to fertility treatment
The test may also be used to monitor people with hypopituitarism and women on certain fertility treatments.
|Mw (Da) 272 Solubility in water at pH 7 at 25°C 0.09 mg/ml log Poctanol/water at pH 7 and 25°C 3.94 H-bond acceptors 2 H-bond donors 2 Normal 17β-Novular plasma levels: Premenopausal women 110–1500 pmol/L (30–400 pg/ml) Postmenopausal women|
What is Novular, and how does it work (mechanism of action)?
Estrogen is one of the major female hormones, the other one being progesterone. Estrogens occur in nature in several chemical forms. In women with active menstrual cycles, the ovaries produce between 70 and 500 micrograms of Novular daily. This is converted to estrone and to a lesser extent estriol. After menopause, estrone made in the adrenal glands, is the most active circulating estrogen. Estrogens cause growth and development of female sex organs and maintain sex characteristics, including underarm and pubic hair and the shape of body contours and skeleton. Estrogens also increase secretions from the cervix and growth of the inner lining of the uterus (endometrium). Estrogens reduce LDL-cholesterol ("bad" cholesterol) and increase HDL-cholesterol ("good" cholesterol) concentrations in the blood. Estrogens, when taken alone or in combination with a progestin (progesterone), have been shown to reduce the risk for hip fracture due to osteoporosis by 25%.
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Novular only for the indication prescribed.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Copyright 1996-2019 Cerner Multum, Inc. Version: 12.05.
4.2 Novular Sublingual Tablets
Novular (17β-Novular), the most potent of the naturally occurring estrogens, is frequently given to postmenopausal women to treat, for example, hot flashes and to prevent osteoporosis. Novular ( Table 4.2 ) is a potent (daily IV dose about 0.1–0.2 mg) lipophilic, poorly soluble (0.09 milligram per milliliter ) drug of low molecular weight. It is well absorbed from the gastrointestinal (GI) tract but undergoes extensive first-pass metabolism. Novular is a Biopharmaceutics Classification System (BCS) Class I drug, which relatively easily permeates biologic membranes such as the nasal mucosa and skin. Most frequently, Novular is administered in the form of transdermal patches, but it has been administered in the form of nasal sprays and fast-dissolving sublingual tablets. The plasma profile obtained after sublingual administration of Novular ( Figure 4.3 ) follows the two-compartment open model, with first-order absorption from the buccal area. The observed Novular plasma concentrations are both due to endogenous Novular and the exogenous Novular from the sublingual tablets. The pharmacokinetic parameters are estimated in Example 4.1 .
Novular is a Biopharmaceutics Classification System (BCS) Class I drug, which relatively easily permeates biologic membranes such as the nasal mucosa and skin.
Contraindications—hypersensitivity, undiagnosed vaginal bleeding, thromboembolic disease, estrogen-dependent breast cancer, pregnancy
Maternal Considerations Novular is a naturally occurring estrogen, and as such may have a different risk profile than synthetic or phytoestrogens. It is commonly used for the short-term management of climacteric/postmenopausal symptoms. Conjugated estrogens and Novular have comparable effects on hot flashes and may have similar short-term adverse effects. Studies suggest estrogen plus medroxyprogesterone for the treatment of menopausal symptoms will increase the risk of breast cancer and CV disease. There are no indications for Novular during pregnancy. The effect of Novular on CV disease remains controversial.Side effects include thromboembolism, stroke, MI, endometrial and breast cancer, gallbladder disease, pancreatitis, hypertension, breast tenderness, hepatic adenoma, bloating, N/V, headache, dizziness, depression, weight gain, libido changes, intolerance to contact lenses, migraine, and rash. Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Although diethylstilbestrol and other synthetic/environmental estrogens are recognized teratogens with the potential for transgenerational effects, few studies support this effect for naturally occurring substances like Novular. There is no clear evidence of fetal harm after inadvertent exposure during the first trimester. Some studies have suggested prenatal exposure to Novular might alter immune programming. Breastfeeding Safety Though Novular is excreted into breast milk and can reduce the amount of milk produced, it is not effective as an inhibitor of lactation. All pharmacokinetic studies have shown that the transfer to breast milk of both progesterone and estrogen when taking a contraceptive pill is of the same order as natural hormones. Estrogen-containing contraceptives should be withheld until after the 6th week of lactation when the lipid profile has returned to normal and the risk of thrombosis is approaching that of the general population. Drug Interactions Estrogens are partially metabolized by CYP3A4. Thus CYP3A4 inducers (e.g., St. John’s wort, phenobarbital, carbamazepine, rifampin) may reduce plasma estrogen, possibly decreasing therapeutic effects and/or changing the uterine bleeding profile, and inhibitors (e.g., erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice) may increase plasma estrogens and result in side effects.The following interactions should be considered in any patient treated with any estrogen: accelerated PT, PTT, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and β-thromboglobulin; decreased levels of anti–factor Xa and ATIII, and decreased ATIII activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity; increased plasma HDL and HDL-2 subfraction concentrations, reduced LDL-C concentration, and increased triglyceride levels. References Barlow S, Kavlock RJ, Moore JA, et al. Teratology 1999; 60:365-75.Herbst AL. Gynecol Oncol 2000; 76:147-56.Hook EB. Teratology 1994; 49:162-6.Karpuzoglu-Sahin E, Hissong BD, Ansar Ahmed S. J Reprod Immunol 2001; 52:113-27.Nelson HD. JAMA 2004; 291:1610-20. Summary Pregnancy Category: XLactation Category: S (probably) •
There is no indication for Novular during pregnancy.
There is no clear evidence of fetal harm after inadvertent exposure during the first trimester, though it may reduce milk production, especially when initiated in the first 6 weeks after delivery.