LABEL REVISIONS: NEW CONTRAINDICATIONS AND WARNINGS
* The labeling of tizanidine cites new contraindications and warnings of serious interactions with fluvoxamine and ciprofloxacin.
* The labeling of bevacizumab will be revised to include data on the risk of tracheoesophageal fistula.
The labeling of tizanidine (Zanaflex) has been revised to include new contraindications and warnings concerning serious drug interactions. Tizanidine, an antispasmodic agent, is an [alpha]2-receptor agonist believed to reduce spasticity-and the increased muscle tone associated with it-by increasing presynaptic inhibition of motor neurons. Tizanidine is metabolized by the cytochrome P-450 isoenzyme CYP1A2. Concurrent administration of tizanidine with potent inhibitors of CYP1A2, such as fluvoxamine (Luvox), a selective serotonin reuptake inhibitor, or ciprofloxacin (Cipro, Ciloxan), an antibiotic, results in significant elevation in serum concentrations of tizanidine, which increases the risk of clinically significant hypotension and sedation. Neither drug should be administered with tizanidine. Although studies of the effects of concomitant administration with CYP1A2 inhibitors other than fluvoxamine and ciprofloxacin have not been conducted, it may be presumed that comparable effects would occur; caution therefore should be used in the concomitant administration of any CYP1A2 inhibitor, such as zileuton (Zyflo), other fluoroquinolones, cimetidine (Tagamet), famotidine (Pepcid), oral contraceptives, acyclovir (Zovirax), antiarrhythmic agents, and ticlopidine. Nurses administering tizanidine should assess whether the patient has also been prescribed any drug that is a CYP1A2 inhibitor.
The labeling of bevacizumab (Avastin) is being revised to reflect new safety information. Bevacizumab is a recombinant humanized monoclonal antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. It is approved for use in the treatment of metastatic cancers of the colon and rectum in combination with the chemotherapeutic drug fluorouracil (Adrucil and others); it's also used in the treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small-cell lung cancer in combination with the chemotherapeutic drugs carboplatin (Paraplatin) and paclitaxel (Onxol, Taxol). In a phase-2 clinical trial of bevacizumab in patients with limited-stage small-cell lung cancer, among the first 29 to whom the drug was administered, there were two confirmed cases and one suspected case of tracheoesophageal fistula; one of the confirmed cases proved fatal. Because of the small sample size in the clinical trial, it's not possible to distinguish the risk of death attributable to bevacizumab from the risk attributable to other factors, such as intrathoracic organ sensitivity resulting from radiation and chemotherapy alone. Bevacizumab has been associated with gastrointestinal tract fistula formation in patients with colorectal cancer and other cancers, and the labeling of the drug will be revised to include the risk of tracheoesophageal fistula. Nurses who believe that a patient has incurred any suspected serious adverse effect of bevacizumab therapy should report it to either the manufacturer or the Food and Drug Administration's MedWatch system (http://www.accessdata.fda.gov/scripts/medwatch).
Acorda Therapeutics. Dear healthcare professional: [letter: updated safety information: contraindications to the use of tizanidine]. 2007 Mar 5. http://www.fda.gov/medwatch/safety/2007/Zanaflex_DHCP_3-27-2007.pdf; Acorda Therapeutics. Prescribing information: Zanaflex [tizanidine hydrochloride]. 2006 Jul. http://www.fda.gov/cder/foi/label/2006/020397s021,021447s002lbl.pdf; Genentech. Dear health care provider: [letter: important drug warning regarding Avastin (bevacizumab)]. 2007 Apr. http://www.fda.gov/medwatch/safety/2007/Avastin_DHCP_TEF_Final_April2007.pdf; Genentech. Final labeling text: Avastin [bevacizumab]. 2006. http://www.fda.gov/cder/foi/label/2006/125085s085lbl.pdf.
TWO DRUGS AFFECTING COAGULATION
* Concentrated protein C has been approved for use in patients who have a severe, potentially life-threatening blood coagulation disorder attributable to a genetic deficiency of endogenous protein C.
* Antihemophilic factor-von Willebrand factor complex has been approved for use in patients with moderate-to-severe von Willebrand disease who are undergoing major surgery.
Ceprotin, or protein C concentrate (human), is the first biologic treatment for patients who have protein C deficiency, a rare genetic defect. Protein C, formed in the liver, prevents the formation and growth of blood clots. When there is an insufficient amount of protein C, potentially life-threatening clotting of blood in vessels occurs throughout the body. Ceprotin is used in patients with severe congenital protein C deficiency to treat purpura fulminans (a severe cutaneous and systemic blood coagulation disorder) and in patients experiencing a life-threatening episode of venous thrombosis. It can also be used prophylactically before surgery or the initiation of anticoagulation therapy to prevent venous thrombosis and purpura fulminans. Administered intravenously, Ceprotin is not intended for daily use, and the patient still needs to take regular doses of anticoagulants once the serious or life-threatening event has resolved. The Food and Drug Administration had granted Ceprotin orphan drug status, which provides incentives to manufacturers in the development of treatments for rare diseases and disorders. The drug is already approved in Europe.
Another biologic product, Humate-P (antihemophilic factor-von Willebrand factor complex), has been approved to prevent excessive bleeding, during and after major surgery, in mild-to-moderate and severe von Willebrand disease, a hereditary bleeding disorder caused by a deficiency in factor VIII and von Willebrand factor. The new indication presents an advantage over a previously approved biological agent for von Willebrand disease, Alphanate (antihemophilic factor [human]), which is not suitable for use in severe disease (see Drug Watch, June).
Now approved to prevent excessive bleeding in patients with mild-to-moderate or severe von Willebrand disease during and after major surgery, the drug was approved originally to treat hemophilia A and later to treat spontaneous, traumatic bleeding in patients with severe von Willebrand disease and for use in mild-to-moderate disease when treatment with desmopressin is ineffective.
Like Alphanate, Humate-P is purified from pooled human plasma of carefully screened and tested U.S. donors and contains the clotting proteins that are either deficient or defective in von Willebrand disease.
Baxter Healthcare Corporation. Prescribing information: Ceprotin [protein c concentrate (human)]. 2007. http://www.fda.gov/cber/label/protbax033007LB.pdf; FDA approves first biologic to treat rare clotting disorder. FDA news 2007 Mar 30. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01598.html; FDA approves product to treat common bleeding disorder. FDA News 2007 Apr 27. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01619.html; Centeon LLC. [Label information:] Antihemophilic factor-von Willebrand factor complex (human), dried, pasteurized Humate-P. 1999. http://www.fda.gov/cber/label/anticen040199LB.pdf.
A NEW INDICATION FOR AN IMMUNE GLOBULIN
* Hepatitis B immune globulin intravenous (human) has been approved for prophylaxis in liver transplantation patients who have a history of hepatitis B.
* The vaccine prevents the recurrence of hepatitis B and consequent loss of the transplanted liver.
Chronic hepatitis can lead to liver failure necessitating transplantation. Infection of the newly transplanted liver can lead to loss of the transplanted organ. Hepatitis B immune globulin intravenous (human) (HepaGam B) has been approved for use as prophylaxis against the recurrence of hepatitis B in liver transplantation patients. HepaGam B is made from the pooled human plasma of healthy donors with high titers of antibodies to hepatitis B surface antigen (anti-HBs). The administration of the first dose of HepaGam B is given concurrently with the liver transplantation (the anhepatic phase). The drug then is administered daily for one week, then once every two weeks for 12 weeks beginning on the 14th day after transplantation. Lifetime monthly infusions of the drug are necessary after the first 12 weeks after transplantation. The vaccine provides passive immunity to those with previous exposure to hepatitis B by binding to hepatitis B surface antigen (HBsAg), reducing the rate of recurrence of hepatitis B. Clinical data submitted to the Food and Drug Administration by the manufacturer showed a decrease in viral recurrence rate from 86% to about 13% in HBsAg-positive liver transplantation patients. HepaGam B was approved in January 2006 as prophylaxis after acute exposure to blood containing HBsAg, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg-positive partners, and household exposure to people with acute hepatitis B infection. Nurses providing care to patients receiving HepaGam B should monitor the serum levels of anti-HBs; an anti-HBs level of at least 500 international units per liter should be achieved within the first week after liver transplantation. Patients who do not attain that level need to receive higher doses of HepaGam B.
Cangene Corp. Prescribing information: HepaGam B [hepatitis B immune globulin intravenous (human). 2007. http://www.fda.gov/cber/label/hbigcan040607LB.pdf; FDA licenses first biologic product to prevent Hepatitis B reinfection in liver transplant patients. FDA News 2007 Apr 6. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01602.html.