Lubion (Progesterone).

Adverse event reporting and prescribing information can be found at the bottom of the page.

What is Lubion?

Lubion is the first1, and only, aqueous progesterone for subcutaneous injection in the UK. It is a water-soluble progesterone in cyclodextrin coating, designed to avoid the need for oil-based solvents, allowing for a subcutaneous injection.

Lubion is indicated for:

Luteal support in adults as part of an ART treatment program in infertile women who are unable to use or tolerate vaginal preparations2.

The Lubion product box

Progesterone as luteal phase support.

Progesterone may be required to sustain pregnancy1.

Low luteal serum progesterone levels are associated with worse clinical outcomes than higher progesterone levels in Assisted Reproductive Technologies (ART)3,4.

A systemic review and meta-analysis of 16 studies demonstrated that among the studies analysing serum progesterone level thresholds <10 ng/ml (31.8nmol/L), a higher serum progesterone level was associated with:

  • Increased rates of ongoing pregnancy or live birth (relative risk (RR) 1.47, 95% confidence interval (Cl) 1.28 to 1.70)
  • Higher chance of clinical pregnancy (RR 1.31, 95% Cl 1.16 to 1.49)
  • Lower risk of miscarriage (RR 0.62, 95% Cl 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst stage embryos5

For patients, Lubion offers the benefits of progesterone treatment, in a subcutaneous administration for patients who are unable to use or cannot tolerate vaginal administration.

A woman making a heart shape with her hands on her pregnancy bump

Efficacy.

A non-inferiority, controlled phase III clinical trial6 in 13 European IVF centres studied the safety and efficacy of Lubion (referred to as Prolutex) compared with Crinone vaginal gel. A total of 683 ART patients were randomised to two groups - 339 patients in the Lubion group and 344 in the Crinone group. The primary end point was ongoing pregnancy rate (OPR) at 10 weeks of treatment.

Method:

  • Lubion dose of 25mg/day administered subcutaneously for 10 weeks
  • Crinone dose of 90mg/day administered vaginally for 10 weeks

Results

  • The OPR was 27.4% vs 30.5%, for Lubion and Crinone respectively (95% CI = 9.91-3.73), indicating noninferiority of Lubion to Crinone.
  • The Live Birth Rate was 26.8% vs 29.9%, for Lubion and Crinone respectively (95% CI = 9.91-3.73), indicating noninferiority of Lubion to Crinone.

Patient safety.

In the study mentioned above, results demonstrated that injecting Lubion for up to 10 weeks was as well tolerated as and comfortable as vaginal progesterone6. Non-serious adverse events were recorded in 42.6% vs 45.64% (p=0.425) of patients receiving Lubion and Crinone, respectively.

Patients treated with Lubion also reported events related to subcutaneous injection as mild8.

Separately, in a small, single-centre, randomised, prospective study in 130 patients undergoing IVF for the first time, intramuscular oily progesterone 33-50mg daily was compared with Lubion 25mg daily in relation to stress hormone (cortisol and prolactin) levels. Results demonstrated that Lubion is associated with lower stress hormone levels than intramuscular progesterone7.

Patient safety data on the water-soluble preparation to date:

  • No reported sterile abscesses
  • No reported severe hypersensitivity reactions2
  • The patient can self-administer in their abdomen or upper thigh and does not have to rely on trained personnel
  • Less vaginal discharge compared to a vaginal preparation (3.85% vs 17.44%, p<0.0001)6
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Safety information.

Contraindications

  • Hypersensitivity to progesterone or to any of the excipients
  • Undiagnosed vaginal bleeding
  • Known missed abortion or ectopic pregnancy
  • Severe hepatic dysfunction or disease
  • Known or suspected breast or genital tract cancer
  • Active or history of, arterial or venous thromboembolism or severe thrombophlebitis
  • Porphyria
  • History of idiopathic jaundice, severe pruritus or pemphigoid gestationis during pregnancy

Adverse events

Very common (≥ 1/10)

  • Uterine spasm
  • Vaginal haemorrhage
  • Administration site reactions

Common (≥ 1/100 to <1/10)

  • Headache
  • Abdominal distension
  • Abdominal pain
  • Nausea
  • Vomiting
  • Constipation
  • Breast tenderness
  • Breast pain
  • Vaginal discharge
  • Vulvo-vaginal pruritus
  • Vulvo-vaginal discomfort
  • Vulvo-vaginal inflammation
  • OHSS
  • Injection site haematoma
  • Injection site induration
  • Fatigue

Refer to the SmPC for details on the full side effect profile, contraindications, warnings and interactions.

Additional resources.

Additional studies.

References

  1. Cometti B. Pharmaceutical and clinical development of a novel progesterone formulation. Acta Obstet Gynecol Scand. 2015;94 Suppl 161:28-37. doi:10.1111/aogs.12765
  2. Lubion Summary of Product Characteristics
  3. Ranisavljevic N, Huberlant S, Montagut M, et al. Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses. Front Endocrinol (Lausanne). 2022;13:892753. Published 2022 Jun 10. doi:10.3389/fendo.2022.892753
  4. González-Foruria I, Gaggiotti-Marre S, Álvarez M, et al. Factors associated with serum progesterone concentrations the day before cryopreserved embryo transfer in artificial cycles. Reprod Biomed Online. 2020;40(6):797-804. doi:10.1016/j.rbmo.2020.03.001
  5. Melo P, Wood S, Petsas G, et al. The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET). Hum Reprod Open. 2022;2022(4):hoac054. Published 2022 Nov 28. doi:10.1093/hropen/hoac054
  6. Lockwood G, Griesinger G, Cometti B; 13 European Centers. Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: a noninferiority randomized controlled study. Fertil Steril. 2014;101(1):112-119.e3. doi:10.1016/j.fertnstert.2013.09.010
  7. Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review. Front Reprod Health. Conforti A, Carbone L, Iorio GG, et al. Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review. Front Reprod Health. 2021;3:634813. Published 2021 Aug 6. doi:10.3389/frph.2021.634813
  8. Allahbadia GN. Has ART Finally Got a Patient-Friendly Progesterone?. J Obstet Gynaecol India. 2015;65(5):289-292. doi:10.1007/s13224-015-0731-8

Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.

Adverse events should also be reported to IBSA Pharma Ltd on 01923 233466 and medicalinformation.uk@ibsagroup.com.