Sirolimus

ArticlesRefrigerated StorageMedicine Compliance Aid StabilityLactation Safety InformationNew Medicines ·
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Articles

Refrigerated Storage

RapamunePfizer Limited

Pfizer Limited
Rapamune
Oral solution, 1mg/mL

In the event of an inadvertent temperature excursion the following data may be used:

If necessary, the patient may store the bottles at room temperature up to 25°C for a short period of time (24 hours), and then put back in a refrigerator at 2°C – 8°C and use the product within 30 days after opening the bottle.

Please refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

Contact Pfizer in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Yes - 30 days (see above)
Yes within 24 hours (see above)
31 December 2020
London MI Service

Medicine Compliance Aid Stability

RapamunePfizer Ltd

Pfizer Ltd
Rapamune
Tablets coated 500 micrograms, 1mg, 2mg
A3 · Amber 3No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Protect from light
Protect from light in an airtight container.
18 September 2015

Lactation Safety Information

See summary
Long half-life increases risk of accumulation in breastfed infants
Low levels anticipated in milk due to the drug's properties
May interfere with lactation
No published evidence of safety
Monitor infant plasma levels if there is a concern about toxicity
16 September 2020

New Medicines

OpsiriaChronic non-infectious, posterior segment uveitis

Information

Opsiria
New formulation
Santen
Santen

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes
Oct 19Still listed in Santen pipeline [13].
Nov 18Still listed in Santen pipeline. Planning to start an additional clinical trial in Nov 18 in the U.S. NDA filed in April 2015 in Asia [11].
Dec 17In the US, a complete response letter was issued indicating the FDA was unable to approve the application and requesting additional substantiating evidence to demonstrate efficacy [10].
Apr 17NDA submitted to FDA [9].
Nov 16Santen is looking at the totality of data from the Sakura programme, and plans to file its NDA to the FDA next year [8].
May 16EU filing withdrawn as the company acknowledged the need to submit additional data on the benefits of Opsiria from an ongoing clinical study [6].
May 16Santen plans to resubmit in Europe [7].
Mar 15Filed in the EU. The EMA has accepted the filing for treatment of noninfectious uveitis (NIU) of the posterior segment, which is supported by data from SAKURA [5].
Oct 12PIII study, SAKURA, (Sirolimus double-masKed Uveitis tReAtment) started May 11 [1].
Oct 12Granted orphan drug status in the US in Nov 11 [3].
Oct 12Granted orphan designation (EU/3/11/898) in the EU Aug 2011 [2].

Category

Inhibits proliferation of activated T-cells by inhibiting cytokine-mediated signal transduction pathways
chronic non-infectious uveitis affects ~ 4.1 in 10,000 people in the EU; equivalent to a total of around 208,000 people [2].
Chronic non-infectious, posterior segment uveitis
Intravitreal

Trial or other data

Jan 21PIII LUMINA study (NCT03711929) is ongoing and has been expanded to include sites in India, South America and Italy. Estimated completion date Jun 22 [14].
Nov 18PIII study (NCT03711929) to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS) starts. There is a 6-month, single-arm, open-label period after completion of the 6-month double- masked, controlled period allows the evaluation of the efficacy and safety of intravitreal injection of DE-109 440 µg every 2 months for longer duration than appropriate for a placebo or sham control. 200 adults will be recruited in the US. Collection of primary outcome data (vitreous haze [VH] of zero response at month 3) is due to complete Feb 21 [12].
Nov 16Santen announces data from PIII SAKURA Study 2. The difference in the effect (of vitreous haze) between the low dose of the drug (44µg) and the 440µg dose was not statistically significant [8].
Apr 14The PIII SAKURA 1 (Study Assessing double‐masKed Uveitis tReAtment) study met its primary endpoint - the proportion of patients achieving a vitreous haze score of zero at month 5 (Standardized Uveitis Nomenclature [SUN] Photographic scale). 347 patients with non-infectious posterior, intermediate or panuveitis were randomized into three treatment arms, each receiving different doses of sirolimus by intravitreal injection. SAKURA Study 2 continues to enroll patients under the same protocol [4].
Oct 12NCT01358266 A PIII multinational, multicentre, randomized, double-masked study of 3 doses of sirolimus for the treatment of 500 patients with active, non-infectious uveitis. The primary outcome is the proportion of subjects with vitreous haze score at 5 months. The study started in May 11 and is due to complete Oct 14 [1].

Evidence based evaluations

Chronic kidney disease - prevention of failed arteriovenous (AV) fistula maturation - implantable collagen matrix

Information

New formulation
Vascular Therapies
Vascular Therapies

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes

Category

Sirolimus is a cell cycle inhibitor, which may prevent hyperplasia and vein stenosis after AV fistula surgery. Single perivascular implant delivered to the vessel wall at and around the site of anastomosis of an AV fistula immediately following surgery.
There were 3,663 first access haemodialysis patients in 2013, 40.7% of which started therapy on an AV fistula [1].
Chronic kidney disease - prevention of failed arteriovenous (AV) fistula maturation - implantable collagen matrix
Implantation

Pachyonychia congenita - topical formulation

Information

New formulation
Palvella Therapeutics
Palvella Therapeutics

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Cream formulation to deliver sirolimus (1%) topically. Sirolimus acts as a ‘mammalian target of rapamycin’ (mTOR) inhibitor to reduce the amount of abnormal keratin preventing formation of blisters and callouses [2].
Pachyonychia congenita (PC) is an ultra-rare inherited, severe and chronically debilitating skin disorder caused by mutations in certain keratin genes. The disorder is manifested by the overproduction of keratin leading to painful conditions including blisters and callouses on the feet that impact mobility, as well as thickened nails, cysts and sores. PC affects <0.01 in 10,000 people in the EU, equivalent to a total of <500 people [2,3]
Pachyonychia congenita - topical formulation
Topical