Theramex launches Bijuva® / Bijuve® (estradiol and progesterone), the first and only body-identical combined hormone therapy treatment for post-menopausal women*

[London, 21 September 2021]: Theramex has today launched Bijuva^® / Bijuve^® (1mg estradiol / 100mg progesterone) across Europe and the UK. Bijuva^®, (known as Bijuve^® in the UK), is the first, and only, body-identical hormone therapy treatment (HRT) for estrogen deficiency symptoms in post-menopausal women with intact uterus and at least 12 months since last menses, which combines estradiol and progesterone in a single daily oral capsule.^1,2 Unlike synthetic hormone products, the estradiol and progesterone found in Bijuva^® / Bijuve^® are chemically and biologically identical to the hormones naturally circulating in the woman’s body.³ 

Real-world evidence, recognised by NICE and the British Menopause Society, suggests that use of body‑identical hormones is associated with lower risks compared to synthetic versions. ^4,5 In particular, the evidence base demonstrates that body-identical hormones have not been shown to increase the risk of venous thromboembolism and are safer forms of HRT with respect to the risk for breast cancer, heart disease, heart attack, and stroke.^6-8

The idea of using body identical hormones to replace estrogens and to protect the endometrium with progesterone appeals to many women⁹. These hormones that many women prefer are now available in a combined single capsule that has been shown to be effective and well-tolerated.^1,9

Dr Paula Briggs, incoming Chair of the British Menopause Society, said, “We know women can be concerned about taking hormones and the impact they may have on their health beyond treating menopause symptoms. The availability of a body-identical progesterone which is well tolerated and has a lower risk profile than oral synthetic progestogens, combined with estradiol in a single capsule, is great news for women.  As a healthcare community we should encourage our patients to reconsider the benefits of newer therapeutic options, allowing them to make informed choices.”

Theramex CEO, Robert Stewart, commented, “For many years menopausal women and their healthcare providers have been seeking an EMA approved body-identical combination therapy. The approval of Bijuva^® / Bijuve^® during Menopause Awareness month represents an important new opportunity for menopausal women suffering from moderate to severe vasomotor symptoms.”

*with intact uterus and at least 12 months since last menses

References

[1] Theramex 2021, Summary of Product Characteristics

² FDA Summary Review. 2018. Available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210132Orig1s000SumR.pdf. Accessed September 2021.

³ Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climateric. 2005;8(Suppl 1):3-63.

⁴ National Institute for Health and Care Excellence. Menopause: diagnosis and management (NG23). 2015. Available at https://www.nice.org.uk/guidance/ng23/. Accessed September 2021.

⁵ British Menopause Society. The British Menopause Society & Women’s Health Concern 2016 recommendations on hormone replacement therapy in menopausal women. 2016. Available at https://thebms.org.uk/publications/consensus- statements/hormone-replacement-therapy/. Accessed September 2021.

⁶ Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy. Postgrad Med. 2009;121(1):73–85.

⁷ Mirkin S. Evidence on the use of progesterone in menopausal hormone therapy. Climateric. 2018;21(4):346-354.

⁸ Fournier A, Berrine F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107:103-111.

⁹ Archer DF, Bernick BA, Mirkin S. A combined, bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause. Expert Rev Clin Pharmacol. 2019;12(8):729–39.

Presentation: Bijuve 1 mg estradiol and 100 mg progesterone soft capsules. Indication: Continuous combined hormone replacement therapy (HRT) for estrogen deficiency symptoms in postmenopausal women with intact uterus and with at least 12 months since last menses. Dosage & administration: The capsule should be taken every day without interruption. Take one capsule each evening with food. For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration should be used. Continuous combined treatment may be started with Bijuve depending on the time since menopause and severity of symptoms. Women experiencing a natural menopause should commence treatment with Bijuve 12 months after their last natural menstrual bleed. For surgically induced menopause, treatment may start immediately. Patients changing from a continuous sequential or cyclical preparation should complete the 28 day cycle and then change to Bijuve. Patients changing from another continuous combined preparation may start therapy at any time. Method of Administration: Oral administration. Contraindications: Known, past or suspected breast cancer. Known or suspected estrogen-dependent malignant tumours (e.g. endometrial cancer). Undiagnosed genital bleeding. Untreated endometrial hyperplasia. Previous or current venous thromboembolism (deep vein thrombosis, pulmonary embolism). Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency). Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction). Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal. Porphyria. Known hypersensitivity to the active substances or to any of the excipients. Special warnings and precautions for use: Before initiating or re-instituting HRT, a complete personal and family medical history should be taken. Conditions which need supervision: If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with Bijuve, in particular: Leiomyoma (uterine fibroids) or endometriosis, risk factors for thromboembolic disorders, risk factors for estrogen dependent tumours e.g. 1st degree heredity for breast cancer, hypertension, liver disorders (e.g. liver adenoma), diabetes mellitus with or without vascular involvement, cholelithiasis, migraine or (severe) headache, systemic lupus erythematosus, a history of endometrial hyperplasia, epilepsy, asthma, otosclerosis. Therapy should be discontinued in cases where a contraindication is discovered and in the following situations: Jaundice or deterioration in liver function, significant increase in blood pressure, new onset of migraine-type headache, pregnancy. Interactions: No drug-drug interaction studies have been conducted with Bijuve. The drug-drug interactions of estradiol and progesterone have been extensively studied and are well established. Both estrogens and progesterone are metabolized via cytochrome P450. Effects of other medicinal products on Bijuve. The metabolism of estrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolizing enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine) and e.g. rifampicin, rifabutin, nevirapine, efavirenz, and griseofulvin. Herbal preparations containing St John's Wort (Hypericum perforatum) may induce the metabolism of estrogens and progestogens. Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Clinically, an increased metabolism of estrogens and progestogens may lead to decreased effect and changes in the uterine bleeding profile. Ketoconazole and other inhibitors of CYP450-3A4 may increase bioavailability of progesterone. Such interactions may increase the incidence of adverse effects such as nausea, breast tenderness, headaches associated with progesterone. Effects of Bijuve on other medicinal products. Hormone contraceptives containing estrogens have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered due to induction of lamotrigine glucuronidation. This may reduce seizure control. Although the potential interaction between HRT and lamotrigine has not been studied, it is expected that a similar interaction exists, which may lead to a reduction in seizure control among women taking both medicinal products together. Progesterone may raise the plasma concentration of ciclosporin. Fertility, Pregnancy and lactation: Not indicated, treatment should be withdrawn immediately. Side effects: The most commonly reported related adverse drug reactions for Bijuve in clinical trials were breast tenderness (10.4%), headache (3.4%), nausea (2.2%), pelvic pain (3.1%), vaginal hemorrhage (3.4%), and vaginal discharge (3.4%). Very Common ADRs (≥ 1/10): Breast tenderness. Common ADRs (≥ 1/100, < 1/10): Abdominal distension, abdominal pain, nausea, fatigue, weight increase, back pain, dizziness, headache, breast pain, pelvic pain, uterine pain/spasm, vaginal discharge, vaginal bleeding haemorrhage, acne, alopecia. Uncommon ADRs (≥ 1/1,000, < 1/100) include: Hypersensitivity, breast cancer, adnexa uteri cyst, paresthesia, parosmia, somnolence, sleep disorder, abnormal dreams, anxiety, depression, insomnia, irritability, mood swings, libido increased, breast disorders, uterine/cervical disorders, endometrial hypertrophy, abnormal biopsy. Package Quantities & Cost: 28 x capsules £8.14 Marketing authorisation number: PL 49876/0015. Marketing authorisation holder: Theramex Ireland Limited, 3rd Floor, Kilmore House, Park Lane, Spencer Dock, Dublin 1, D01 YE64, Ireland. Legal classification: POM. Date of Preparation: May 2021: Bijuva_GB_PI_003990.