ABSTRACT
PURPOSE: To assess the safety of a highly purified, plasma-derived factor VIII concentrate (Replenate) in routine clinical use. METHODS: Following guidelines entitled safety assessment of marketed medicines (SAMM), safety data were collected in the UK on 194 patients who received an estimated 47.6 million IU of Replenate. This population included 47 patients undergoing 53 surgical operations or dental extractions. RESULTS: The study detected four cases of new factor VIII inhibitor development and twelve other adverse events, five that were unrelated to the product, five whose causality was unknown, one that was possibly product-related and one case due to possible lack of efficacy. Only one of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. Three patients were switched from Replenate as a result of an adverse event (one case of infusion site irritation and two cases of a rise in titre of an existing inhibitor), but no unexpected adverse reactions were noted and there were no reports of virus transmission. The median factor VIII recovery value was 2.17 IU/dl per IU/kg, but recovery was shown to be dependent on several variables, namely inhibitor status, treatment centre and the patient's body weight. The median factor VIII recovery in inhibitor-free patients was 2.28 IU/dl per IU/kg (range: 1.20-6.62). CONCLUSIONS: The study confirms that Replenate is well tolerated by the majority of patients in routine clinical practice.
Subject(s)
Factor VIII/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Colectomy , Craniotomy , Cross-Sectional Studies , Female , Hepatitis Viruses/isolation & purification , Humans , Laparotomy , Male , Middle Aged , Retrospective Studies , Safety , Surveys and QuestionnairesABSTRACT
PURPOSE: To assess the safety of a plasma-derived highly purified factor IX concentrate (Replenine) in routine clinical use. METHODS: Following guidelines entitled Safety Assessment of Marketed Medicines (SAMM), safety data were collected in the UK by retrospective review of the hospital notes of 114 patients who received an estimated 14.8 million IU of Replenine. Included were 40 patients undergoing 44 surgical procedures or dental extractions [corrected]. RESULTS: The study detected a total of nine adverse events (AEs), four of which were possibly product-related, four that were unrelated to the product and one whose causality was unknown. None of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. One patient was switched from Replenine because of infusion site irritation, but no unexpected adverse reactions were noted. There were no reports of virus transmission or new factor IX inhibitor development. The mean factor IX recovery value was 1.44 IU/dl per IU/kg (95%CI: 1.31-1.57 IU/dl per IU/kg). CONCLUSIONS: The study was a practical application of the SAMM guidelines to the collection of pharmacovigilance data on patients with Haemophilia B. Replenine is well tolerated in routine clinical practice.
Subject(s)
Factor IX/adverse effects , Product Surveillance, Postmarketing , Retrospective Studies , Adult , Data Collection/methods , Demography , Drug Administration Schedule , Factor IX/administration & dosage , Factor IX/therapeutic use , Female , Hemophilia A/blood , Hemophilia A/complications , Hemophilia A/drug therapy , Hemophilia B/blood , Hemophilia B/complications , Hemophilia B/drug therapy , Humans , Infusions, Intravenous , Injections, Intravenous , Male , Patient Selection , Pharmacology, Clinical , Surgical Procedures, Operative/classification , Surveys and Questionnaires , Treatment Outcome , United Kingdom , Virus Diseases/complications , Virus Diseases/diagnosis , Virus Diseases/drug therapyABSTRACT
BACKGROUND AND OBJECTIVES: The tolerability and pharmacokinetics of a solvent/detergent-treated intramuscular immunoglobulin were compared with those of the standard product. MATERIALS AND METHODS: Single, 750-mg intramuscular (i.m.) injections were administered to a total of 36 healthy individuals: 23 in a double-blind trial and 13 in an open trial. Changes in specific serum hepatitis A and hepatitis B antibodies were monitored for a period of up to 3 months postinjection. RESULTS: No serious adverse reactions were reported, and the bioavailability of the solvent/detergent-treated preparation was equivalent to that of the standard i.m. immunoglobulin. CONCLUSION: There is no evidence that solvent/detergent treatment alters the pharmacokinetics or tolerance of human normal immunoglobulin, but it offers additional assurance against potential virus transmission.
Subject(s)
Detergents/pharmacology , Immunoglobulins, Intravenous/isolation & purification , Solvents/pharmacology , Adolescent , Adult , Aged , Area Under Curve , Biological Availability , Double-Blind Method , Female , Hepatitis A Antibodies , Hepatitis Antibodies/blood , Hepatitis B Antibodies/blood , Humans , Immunization, Passive , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , Immunoglobulins, Intravenous/drug effects , Immunoglobulins, Intravenous/pharmacokinetics , Injections, Intramuscular , Male , Middle Aged , Organophosphates/administration & dosage , Organophosphates/pharmacology , SafetyABSTRACT
It has been found that in BHK 21 cells caffeine potentiates cell killing by both UV irradiation and N-methyl-N-nitrosoguanidine (MNNG). The potentiating effect is greater with UV than with MNNG. While non-toxic concentrations of caffeine inhibit the joining of newly-replicated DNA fragments into large molecular weight DNA (post-replication repair) after UV irradiation, they have no such effect after MNNG treatment. Furthermore, the joining of DNA fragments continues in the cells treated with 3 microgram/ml of MNNG, a dose which leads to less than 5% cell survival. While inhibition of the synthesis of large molecular weight DNA can explain the synergistic effect of caffeine upon cell survival after UV irradiation, it cannot explain the similar effect after MNNG treatment.
