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GREENSTONE LLC INTRODUCES SIROLIMUS TABLETS
Authorized Generic of RAPAMUNE®

PEAPACK, N.J., November 2014 — Greenstone LLC, a U.S.-based generic pharmaceutical subsidiary of Pfizer Inc. (NYSE: PFE), announced, on October 27, 2014, the introduction of sirolimus tablets to its ever-expanding generic pharmaceutical product line. The product is offered as 1 mg and 2 mg tablets in bottles of 100 tablets each.

Greenstone’s sirolimus tablets product is the authorized generic of, and equivalent to the innovator’s product, RAPAMUNE® (sirolimus tablets). This new authorized generic adds to Greenstone’s consistently growing line of products, and is backed by the distribution and customer service support of Pfizer Inc., one of the world’s premiere biopharmaceutical companies. As a subsidiary of Pfizer, Greenstone operates under the same values and commitment to bring quality authorized generics to customers, payers, and the patients it serves.

See the Full Prescribing Information, including boxed warning, for Greenstone’s Sirolimus at http://www.greenstonellc.com/product-list.aspx. For more information about Greenstone LLC and its products, visit http://greenstonellc.com.

Rapamune® is a registered trademark of Wyeth LLC.

Indication

SIROLIMUS is an immunosuppressive agent indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants. Therapeutic drug monitoring is recommended for all patients receiving SIROLIMUS.

  • In patients at low-to moderate-immunologic risk, it is recommended that SIROLIMUS be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation.
  • In patients at high-immunologic risk, it is recommended that SIROLIMUS be used in combination with cyclosporine and corticosteroids for the first year following transplantation. Safety and efficacy of CsA withdrawal has not been established in high risk patients.

Important Safety Information

BOX WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS

  • Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression.

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use SIROLIMUS. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

  • The safety and efficacy of SIROLIMUS as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended.
  • Liver Transplantation – Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis (HAT)

The use of SIROLIMUS in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.

In this and another study in de novo liver transplant patients, the use of SIROLIMUS in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death.

  • Lung Transplantation – Bronchial Anastomotic Dehiscence

Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when SIROLIMUS has been used as part of an immunosuppressive regimen.

  • SIROLIMUS is contraindicated in patients with a hypersensitivity to SIROLIMUS. Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis and hypersensitivity vasculitis have been associated with SIROLIMUS.
  • SIROLIMUS has been associated with the development of angioedema. Concomitant use of SIROLIMUS with other drugs known to cause angioedema, such as ACE-inhibitors, may increase the risk of developing angioedema.
  • There have been reports of impaired or delayed wound healing in patients receiving SIROLIMUS, including lymphocele and wound dehiscence. Appropriate measures should be considered to minimize such complications. There have also been reports of fluid accumulation, including peripheral edema, lymphedema, pleural effusion, ascites, and pericardial effusions including hemodynamically significant effusions and tamponade requiring intervention.
  • In clinical trials, up to 90% of patients required treatment for hyperlipidemia and hypercholesterolemia with anti-lipid therapy. Despite anti-lipid management, up to 50% of patients had fasting serum cholesterol levels >240 mg/dL and triglycerides above recommended target levels. Any patient who is administered SIROLIMUS should be monitored for hyperlipidemia.
  • Renal function should be closely monitored during the co-administration of SIROLIMUS with cyclosporine because long-term administration of the combination has been associated with deterioration of renal function.
  • Periodic quantitative monitoring of urinary protein excretion is recommended because increased urinary protein excretion, including nephrotic range proteinuria, has been observed following conversion from a calcineurin inhibitor (CNI) to SIROLIMUS. The safety and efficacy of conversion from a CNI to SIROLIMUS in maintenance renal transplant recipients have not been established.
  • Immunosuppressed patients are at increased risk for opportunistic infections, including activation of latent viral infections. BK virus-associated nephropathy and cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been observed in patients receiving immunosuppressants, including SIROLIMUS.
  • Cases of interstitial lung disease (including pneumonitis, bronchiolitis obliterans organizing pneumonia, and pulmonary fibrosis), some fatal, with no identified infectious etiology have occurred in patients receiving immunosuppressive regimens including SIROLIMUS.
  • The safety and efficacy of de novo use of SIROLIMUS without cyclosporine is not established in renal transplant patients.
  • The concomitant use of SIROLIMUS with a CNI may increase the risk of CNI-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy.
  • Concomitant use of SIROLIMUS with strong inhibitors or inducers of should be avoided. Caution should be exercised when administering with CYP3A4/P-gp inhibitors or inducers.
  • Antimicrobial prophylaxis for Pneumocystis carinii pneumonia should be administered for 1 year following transplantation. Cytomegalovirus (CMV) prophylaxis is recommended for 3 months after transplantation.
  • Patients on immunosuppressive therapy are at increased risk for skin cancer. Exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.
  • SIROLIMUS is a Pregnancy Category C drug. There are no adequate and well-controlled studies in pregnant women. Effective contraception must be initiated before SIROLIMUS therapy, during SIROLIMUS therapy, and for 12 weeks after SIROLIMUS therapy has been stopped. SIROLIMUS should be used during pregnancy only if the potential benefit outweighs the potential risk to the embryo/fetus.
  • It is not known whether sirolimus is excreted in human milk. The pharmacokinetic and safety profiles of sirolimus in infants are not known. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
  • The safety and efficacy of sirolimus in pediatric patients < 13 years have not been established.
  • In general, adverse events related to the administration of SIROLIMUS were dependent on dose/concentration. The most common (≥ 30%) adverse reactions are:
  • peripheral edema
  • hypertriglyceridemia
  • hypertension
  • hypercholesterolemia
  • creatinine increased
  • thrombocytopenia
  • constipation
  • abdominal pain
  • diarrhea
  • headache
  • fever
  • urinary tract infection
  • anemia
  • nausea
  • arthralgia
  • Pain
  • The following adverse reactions resulted in a rate of discontinuation of > 5% in clinical trials:
  • creatinine increased
  • hypertriglyceridemia
  • thrombotic thrombocytopenic purpura (TTP)