Meningococcal quadrivalent (serogroups A, C, W135 and Y) tetanus toxoid conjugate vaccine (Nimenrix™).

Nimenrix™ (MenACWY-TT) is a quadrivalent meningococcal conjugate vaccine, comprising the polysaccharide serogroups A, C, W135 and Y, and tetanus toxoid (TT) as carrier protein. It is the first quadrivalent vaccine (administered as a single dose) to be approved in Europe for active immunization of individuals aged ≥ 12 months against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W135 and Y. Administration of a single dose of Nimenrix™ elicited a strong immune response against all four vaccine serogroups in healthy toddlers aged 12-23 months, children and adolescents aged 2-17 years and adults aged 18-55 years in randomized, multicentre, phase III trials. In toddlers, Nimenrix™ was noninferior to Meningitec® in terms of seroresponse rates against meningococcal serogroup C 42 days post-vaccination. In children, adolescents and adults, Nimenrix™ was noninferior to Mencevax™ in terms of vaccination response rates against all four serogroups 1 month post-vaccination. Furthermore, several phase II studies and a phase III trial showed that the immune response elicited by Nimenrix™ in all age groups persisted for 7-42 months after the primary vaccination (when evaluated by rabbit serum bactericidal activity), with the vaccine also inducing immune memory in toddlers. In addition, several randomized, multicentre, phase III, noninferiority trials showed that when coadministered with other childhood vaccines or a seasonal flu vaccine, the immunogenicity of Nimenrix™ or that of the coadministered vaccine was generally not altered. Nimenrix® was generally well tolerated in all age groups whether administered as a single vaccine or coadministered with other routine vaccines. The incidence of grade 3 local or systemic solicited adverse events during the first 4 days following vaccination and of serious adverse events over an extended follow-up period of up to 6 months was low (<4.5%). Although protective effectiveness and longer-term persistence studies are required, current evidence suggests that Nimenrix™, administered as a single dose, provides a valuable vaccination option for the prevention of meningococcal disease across a broad age group, including children as young as 12 months.

Ulipristal acetate: in uterine fibroids.

Ulipristal acetate, a selective progesterone-receptor modulator, inhibits the proliferation and induces apoptosis of leiomyoma cells in vitro. It also modulates the expression of vascular endothelial growth factors and hormone receptors and modulates extracellular matrix breakdown in leiomyoma cells but not in myometrial cells. In two randomized, double-blind, multinational phase III trials of 13 weeks' duration in women aged 18-50 years with uterine fibroids, a once-daily regimen of oral ulipristal acetate 5 mg/day controlled excessive uterine bleeding (primary endpoint) in ≥90% of patients. Ulipristal acetate 5 mg/day was more effective than placebo and was shown to be noninferior to intramuscular leuprolide acetate 3.75 mg once monthly in controlling uterine bleeding. Uterine bleeding was rapidly controlled by ulipristal acetate. Approximately half of recipients of ulipristal acetate 5 mg/day became amenorrhoeic within the first 10 days of treatment. Furthermore, uterine bleeding was controlled significantly more rapidly for recipients of ulipristal acetate than recipients of leuprolide acetate. A significantly greater median reduction from baseline in total fibroid volume was observed for recipients of ulipristal acetate 5 mg once daily than recipients of placebo following 13 weeks' treatment (coprimary endpoint). For patients who did not undergo surgery, the volume reduction was maintained for at least 6 months after discontinuing treatment. Ulipristal acetate was generally well tolerated in women with uterine fibroids. The incidence of hot flush occurred with a significantly lower frequency for recipients of ulipristal acetate than for recipients of leuprolide acetate.

Etravirine: a review of its use in the management of treatment-experienced patients with HIV-1 infection.

Etravirine (Intelence®) is an orally administered next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). It is approved for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and are harbouring HIV-1 strains resistant to other antiretroviral (ARV) agents. In the US, etravirine must be used in combination with other ARV agents; in the EU, it must be used in combination with other ARV agents that include a boosted HIV-1 protease inhibitor. Etravirine shows good activity in vitro against most wild-type strains of HIV-1, as well as against several strains resistant to available NNRTIs. Furthermore, etravirine appears to present a higher barrier than first-generation NNRTIs against the development of drug resistance. Whereas the presence of a single mutation is sufficient to affect the virological response to efavirenz or nevirapine, the resistance profile of etravirine is more complex and a prediction of virological response may be calculated using a weighted genotypic score. Importantly, the most prevalent NNRTI-associated mutation, K103N, alone does not affect the etravirine response. In two identically designed randomized clinical trials, the addition of etravirine to an optimized background therapy (OBT) regimen improved virological responses to a greater extent than placebo plus OBT following 24 weeks' treatment in highly treatment-experienced adult patients with HIV-1 infection who had evidence of viral replication (HIV-1 RNA levels of >5000 copies/mL at baseline). Furthermore, pre-planned pooled analyses of the trials at 48 and 96 weeks showed that etravirine plus OBT provided durable virological suppression. Consistently higher virological response rates were observed for recipients of etravirine plus OBT than placebo plus OBT in a pre-specified subgroup analysis of baseline viral loads, CD4+ cell counts, HIV-1 subtype or the composition of background ARV therapy. Greater improvements from baseline in immunological outcomes were also observed for recipients of etravirine plus OBT compared with those receiving placebo plus OBT over the 96-week treatment period of the trials. When used as part of an OBT regimen in trials of up to 96 weeks duration, etravirine was well tolerated with an overall tolerabilty profile similar to that of placebo. The only treatment-emergent adverse event that occurred with a higher frequency for recipients of etravirine compared with placebo plus OBT was rash. In highly treatment-experienced patients with HIV-1 infection and evidence of viral replication, the addition of etravirine to an OBT regimen provides an effective and well tolerated treatment that leads to improvements in both virological and immunological outcomes.

Valsartan: in children and adolescents with hypertension.

Valsartan is an oral angiotensin II subtype 1 receptor antagonist with well established antihypertensive efficacy in adults. It is now approved in the EU and the US for the treatment of hypertension in children and adolescents. In two, randomized, double-blind trials, a once-daily regimen of valsartan reduced the blood pressure (BP) of children and adolescents with hypertension. In one trial in hypertensive children and adolescents aged 6-16 years, significant dose-dependent reductions from baseline in mean sitting systolic BP (msSBP) were observed for recipients of valsartan following 2 weeks' treatment (primary endpoint). There were corresponding dose-dependent and significant reductions in mean sitting diastolic BP. Following 2 further weeks of treatment, the reduction in msSBP was maintained in patients who were re-randomized to continue receiving the same dosage of valsartan but not in those re-randomized to placebo. In the other trial in hypertensive children and adolescents aged 6-17 years, valsartan was no less effective than enalapril in reducing BP. Following 12 weeks' treatment, the least square mean reduction from baseline in msSBP (primary endpoint) in recipients of valsartan was noninferior to that in recipients of enalapril. In addition, the proportion of patients achieving an msSBP <95th percentile for age, sex, and height at week 12 was not significantly different between recipients of valsartan and enalapril (67% vs 70%). Treatment with valsartan for up to 52 weeks was well tolerated in children and adolescents with hypertension.

Aripiprazole: a review of its use in the management of schizophrenia in adults.

Oral aripiprazole (Abilify®) is an atypical antipsychotic agent that is approved worldwide for use in adult patients with schizophrenia. It is a quinolinone derivative that has a unique receptor binding profile as it exhibits both partial agonist activity at dopamine D(2) receptors and serotonin 5-HT(1A) receptors and antagonist activity at 5-HT(2A) receptors. In several well designed, randomized, clinical trials of 4-6 weeks duration, aripiprazole provided symptomatic control for patients with acute, relapsing schizophrenia or schizoaffective disorder. Furthermore, following 26 weeks' treatment, the time to relapse was significantly longer for patients with chronic, stabilized schizophrenia receiving aripiprazole compared with those receiving placebo. Using a variety of efficacy outcomes, aripiprazole showed a mixed response when evaluated against other antipsychotic agents in randomized clinical trials. Longer-term data showed that improvements in remission rates and response rates favoured aripiprazole over haloperidol, although, the time to failure to maintain a response was not significantly different between the treatment arms. On the other hand, improvements in positive and negative symptom scores mostly favoured olanzapine over aripiprazole, although, the time to all-cause treatment discontinuation was not significantly different between the two treatments. Several open-label, switching trials showed that aripiprazole provided continued control of symptoms in patients with schizophrenia or schizoaffective disorder. Using a variety of efficacy outcomes or quality-of-life scores, longer-term treatment generally favoured patients switched to receive aripiprazole compared with standard-of-care oral antipsychotics. Aripiprazole was generally well tolerated in patients with schizophrenia. In particular, its use seems to be associated with a lower incidence of extrapyramidal symptoms than haloperidol and fewer weight-gain issues than olanzapine. Aripiprazole also showed a favourable cardiovascular tolerability profile and its use was associated with a reduced risk of metabolic syndrome than placebo or olanzapine. As a consequence, aripiprazole may provide a more cost-effective treatment option compared with other atypical antipsychotics. In conclusion, oral aripiprazole provides an effective and well tolerated treatment alternative for the acute and long-term management of patients with schizophrenia.

Spotlight on ustekinumab in moderate to severe plaque psoriasis.

Ustekinumab (Stelara™) is a human monoclonal antibody that binds to the p40 subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US for use in adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In the EU, it is indicated for those who failed to respond to, have a contraindication to, or are intolerant of other systemic therapies or phototherapy. In well designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or 90 mg provided a rapid and durable improvement in Psoriasis Area and Severity Index scores for patients with moderate to severe plaque psoriasis. Treatment with ustekinumab 45 or 90 mg also improved health-related quality-of-life scores from baseline. More limited data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in clinical trials; most adverse events were mild in intensity and did not require dosage adjustment. A pooled analysis of clinical trial data indicated no specific patterns of infection for recipients of ustekinumab and that infection rates remained stable following cumulative exposure to the agent. Thus, subcutaneous ustekinumab provides an effective and well tolerated alternative for the symptomatic treatment of patients with moderate to severe plaque psoriasis.

Ustekinumab: a review of its use in the management of moderate to severe plaque psoriasis.

Ustekinumab (Stelara™) is a human monoclonal antibody that binds to the p40 subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US for use in adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In the EU, it is indicated for those who failed to respond to, have a contraindication to or are intolerant of other systemic therapies or phototherapy. This article reviews the efficacy and tolerability of ustekinumab in patients with moderate to severe plaque psoriasis, as well as summarizing its pharmacological properties. Ustekinumab attenuates the immune cell activation properties of IL-12 and IL-23. It interrupts the abnormal activation of signalling and cytokine cascades that underlie the pathology of psoriasis by reducing the expression of IL-12- and IL-23-induced cell surface markers that mediate skin homing, activation and cytokine release. In well designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or 90 mg provided a rapid and durable improvement in psoriasis area severity index (PASI) scores for patients with moderate to severe plaque psoriasis. A significantly greater proportion of patients receiving ustekinuman 45 or 90 mg compared with those receiving placebo achieved a ≥75% improvement from baseline in PASI score following 12 weeks' treatment (primary endpoint). Improvements in PASI scores were evident following 2 weeks' treatment with ustekinumab and were sustained for up to 3 years. Treatment with ustekinumab 45 or 90 mg also improved health-related quality-of-life scores from baseline. Following 12 weeks' treatment, ustekinumab 45 or 90 mg was more effective than etanercept 50 mg twice weekly in providing symptomatic relief for patients with moderate to severe plaque psoriasis. Furthermore, ustekinumab treatment provided effective symptomatic improvement for almost half of the patients who showed no response to 12 weeks' treatment with etanercept. More limited data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in clinical trials; most adverse events were mild in intensity and did not require dosage adjustment. A pooled analysis of clinical trial data indicated no specific patterns of infection for recipients of ustekinumab and that infection rates remained stable following cumulative exposure to the agent. In conclusion, subcutaneous ustekinumab provides an effective and well tolerated alternative for the symptomatic treatment of patients with moderate to severe plaque psoriasis.

Clonidine extended-release: in attention-deficit hyperactivity disorder.

Clonidine, an α(2)-adrenergic agonist, is approved in the US as an extended-release (XR) tablet for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents (aged 6-17 years). In two, randomized, double-blind, multicenter, phase III trials of 8 weeks' duration, clonidine XR improved the symptoms of ADHD in children and adolescents. Significantly greater reductions from baseline in ADHD rating scale IV (ADHD-RS-IV) total scores at week 5 (primary endpoint) were achieved by recipients of clonidine XR 0.2 and 0.4 mg/day monotherapy than by recipients of placebo. When added to patients' normal stimulant regimen, significantly greater reductions from baseline in ADHD-RS-IV total scores at week 5 (primary endpoint) were achieved with a flexible dose of clonidine XR 0.1-0.4 mg/day than with placebo. Symptomatic improvement of ADHD was achieved following 2 weeks' treatment with clonidine XR. In both trials, significantly greater reductions from baseline in ADHD-RS-IV total scores were apparent at week 2 onwards for recipients of clonidine XR than for recipients of placebo. Clonidine XR was generally well tolerated as monotherapy and as adjunctive therapy with stimulant regimens in clinical trials in children and adolescents.

Corifollitropin alfa: a review of its use in controlled ovarian stimulation for assisted reproduction.

Corifollitropin alfa (Elonva®) is a fusion product of human follicle-stimulating hormone (FSH) and the C-terminal peptide of the ß-subunit of human chorionic gonadotropin (hCG) produced by recombinant DNA technology. It has the same pharmacologic activity as FSH and recombinant FSH (rFSH; follitropin alfa; follitropin beta), but with a slower absorption and a longer half-life. Corifollitropin alfa is indicated as a multifollicular stimulant for women undergoing controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist-assisted reproduction protocols. In two large, randomized, double-blind, phase III trials, a single subcutaneous injection of corifollitropin alfa was no less effective as a multifollicular stimulant than seven once-daily injections of rFSH when used as part of a GnRH antagonist-assisted controlled ovarian stimulation cycle. With regard to primary endpoints, the mean number of retrieved oocytes per started cycle demonstrated that the two treatments were equivalent, and the ongoing pregnancy rate in recipients of corifollitropin alfa was noninferior to that in recipients of rFSH. The median duration of stimulation with FSH was 9 days in both treatment arms of both trials, which means that, on average, recipients of corifollitropin alfa required only 2 further days of stimulation with rFSH prior to triggering oocyte maturation with the administration of hCG. Fertilization rates were high, ranging from 66% to 68%, in recipients of corifollitropin alfa or rFSH in both trials. When used as part of a GnRH antagonist-assisted reproduction protocol, corifollitropin alfa was generally well tolerated, with a tolerability profile similar to that of rFSH. In large, pooled analyses of clinical trials, the incidence of ovarian hyperstimulation syndrome in both the corifollitropin alfa and rFSH treatment arms was consistent with that expected in the relatively young patient population. Furthermore, there were no clinically relevant differences in pregnancy complications and the incidence of infant adverse events between treatment arms. In conclusion, a single subcutaneous injection of corifollitropin alfa provides sustained multifollicular stimulation for up to a week in women undergoing controlled ovarian stimulation. Compared with seven once-daily injections of rFSH, a single injection of corifollitropin alfa achieves equivalent efficacy, and provides a well tolerated and more convenient treatment option to induce multiple follicular growth prior to assisted reproduction.

Rituximab: as first-line maintenance therapy following rituximab-containing therapy for follicular lymphoma.

Rituximab is a recombinant chimeric murine/human monoclonal IgG(1-κ) antibody. It binds specifically to the CD20 antigen on normal and malignant B lymphocytes and produces complement-dependent and antibody-dependent cytotoxicity and induces apoptosis in these cells. Prolonged treatment with rituximab in patients with follicular lymphoma results in a sustained reduction in circulating B lymphocytes. Two years of single-agent maintenance therapy with rituximab significantly prolonged progression-free survival (primary endpoint) compared with observation in patients with follicular lymphoma who were responsive to first-line induction therapy with rituximab plus chemotherapy. Furthermore, maintenance therapy with rituximab significantly delayed the time to the next antilymphoma treatment and the next chemotherapy compared with observation in these patients. Rituximab had an acceptable tolerability profile as single-agent maintenance therapy in patients with follicular lymphoma with no new or unexpected adverse events compared with induction therapy.

Ulipristal acetate: a review of its use in emergency contraception.

Ulipristal acetate (ellaOne®; ella®) is the first of a new class of selective progesterone receptor modulators, and is indicated for emergency contraception within 120 hours after unprotected sexual intercourse or contraceptive failure. The principal effect of ulipristal acetate is to inhibit or delay ovulation. This effect may result from the drug's ability to delay the onset of luteinizing hormone (LH) surge or postpone LH peak if LH surge has started, or possibly by a direct inhibitory effect on follicular rupture, when administered in the follicular phase (including just before ovulation). In clinical trials, a single oral dose of ulipristal acetate 30 mg was effective in preventing pregnancies in women requesting emergency contraception after unprotected sexual intercourse and provided sustained efficacy throughout the 120-hour postcoital period in which it is indicated. When compared with levonorgestrel in well designed noninferiority trials, it was no less effective in preventing pregnancies when administered within 72 hours of unprotected intercourse, but was more effective when administered later (within 72-120 hours). Results of a meta-analysis suggest that ulipristal acetate may be more effective than levonorgestrel from day 1 and throughout the entire 5-day period following unprotected sexual intercourse. Ulipristal acetate is generally well tolerated, with a similar tolerability profile to that of levonorgestrel. In general, the onset of menses is delayed by 2-3 days following treatment. Although, ulipristal acetate is more expensive than levonorgestrel, it may represent a cost-effective alternative to levonorgestrel for women requesting emergency contraception within 120 hours of unprotected intercourse. Thus, ulipristal acetate provides effective, sustained and well tolerated emergency contraception when taken within 120 hours of unprotected sexual intercourse, thereby offering an extended treatment window compared with levonorgestrel, which should be administered within 72 hours.

Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers).

Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%. A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days. Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.

Fulvestrant: a review of its use in the management of hormone receptor-positive metastatic breast cancer in postmenopausal women.

Fulvestrant (Faslodex®) is an intramuscularly administered steroidal estrogen receptor antagonist that is devoid of any known estrogen agonist effects. It is indicated as second-line therapy for the treatment of postmenopausal women with hormone receptor-positive advanced breast cancer who have progressed following prior endocrine therapy. In well designed, randomized clinical trials, regimens of fulvestrant 250 and 500 mg provided effective second-line therapy for postmenopausal women with advanced breast cancer who had progressed following prior endocrine therapy. Moreover, fulvestrant 250 mg monthly (with or without a loading dose) was as effective as aromatase inhibitor therapy. However, fulvestrant is absorbed slowly, and greater steady-state concentrations are achieved more rapidly when using a higher dosage with a loading dose regimen. Consequently, a regimen of fulvestrant 500 mg monthly with a loading dose was significantly more effective than a regimen of 250 mg monthly in postmenopausal women with disease progression. Limited data also indicate a potential role for the fulvestrant 500 mg regimen as first-line therapy. Fulvestrant is generally well tolerated with no additional adverse events noted with the high-dose regimen compared with the 250 mg regimens. Furthermore, the incidence of joint disorders was shown to be significantly lower with fulvestrant 250 mg monthly than with anastrozole. Treatment with fulvestrant is not associated with any clinically significant effects on endometrial thickening, bone-specific turnover markers or sex hormone levels. In conclusion, a monthly regimen of intramuscular fulvestrant 500 mg with a loading dose provides effective and well tolerated second-line therapy for postmenopausal women with advanced breast cancer who have progressed following prior endocrine therapy and is now the approved optimal dose.

Trastuzumab: in HER2-positive metastatic gastric cancer.

Trastuzumab is a recombinant humanized IgG1 monoclonal antibody directed against the extracellular domain of the human epidermal growth factor receptor type 2 (HER2) that inhibits HER2-dependent tumour cell proliferation and survival. Proliferation of gastric cancer cells overexpressing HER2 is inhibited by trastuzumab in vitro and in vivo. HER2-positive expression (defined as immunohistochemistry 3+ or fluorescence in situ hybridization-positive) was observed in 22.1% of almost 4000 metastatic gastric cancers in patients who were screened for randomization in the open-label, multicentre, phase III ToGA trial. In patients with HER2-positive metastatic gastric cancer (n = 584), median overall survival (primary endpoint) was significantly longer for recipients of intravenous trastuzumab plus chemotherapy (comprising cisplatin and either fluorouracil or capecitabine) than in those receiving chemotherapy alone in the ToGA trial. Furthermore, the overall response rate was significantly higher and the median time to disease progression and median time of progression-free survival were also significantly longer with trastuzumab plus chemotherapy than with chemotherapy alone. In general, combination therapy with trastuzumab and chemotherapy was relatively well tolerated in patients with metastatic gastric cancer with no reports of new or unexpected adverse events.

Lidocaine/tetracaine medicated plaster: in minor dermatological and needle puncture procedures.

The lidocaine/tetracaine medicated plaster comprises a lidocaine/tetracaine 70 mg/70 mg patch and a controlled heat-assisted drug delivery pod that increases the diffusion of lidocaine and tetracaine into the dermis. Following a 1-hour application period, systemic absorption of lidocaine or tetracaine from the plaster was minimal. The lidocaine/tetracaine medicated plaster provided effective pain relief for adult (including elderly) patients undergoing minor dermatological procedures and for adult and paediatric patients undergoing vascular access procedures. In randomized, double-blind clinical trials, patient-reported median pain scores were significantly lower with the lidocaine/tetracaine medicated plaster than with an identical plaster containing placebo in patients undergoing minor dermatological or vascular access procedures. Furthermore, patient-reported median pain scores were significantly lower with the lidocaine/tetracaine medicated plaster than with a lidocaine/prilocaine cream in patients undergoing vascular access procedures. In a large, randomized, double-blind trial in paediatric patients undergoing venipuncture, the overall incidence of pain was significantly lower with the lidocaine/tetracaine medicated plaster than with a lidocaine/prilocaine plaster. The lidocaine/tetracaine medicated plaster was well tolerated, with the most frequent treatment-related adverse events resolving spontaneously.

Lopinavir/Ritonavir: a review of its use in the management of HIV-1 infection.

Lopinavir/ritonavir (Kaletra®) is an orally administered coformulated ritonavir-boosted protease inhibitor (PI) comprising lopinavir and low-dose ritonavir. It is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults, adolescents and children. Lopinavir/ritonavir is available as a tablet, soft-gel capsule and an oral solution for patients with difficulty swallowing. In well designed, randomized clinical trials, lopinavir/ritonavir, in combination with other antiretroviral therapies (ART), provided durable virological suppression and improved immunological outcomes in both ART-naive and -experienced adult patients with virological failure. Furthermore, lopinavir/ritonavir demonstrated a high barrier to the development of resistance in ART-naive patients. More limited data indicate that it is effective in reducing plasma HIV-1 RNA levels in paediatric patients. Lopinavir/ritonavir has served as a well established benchmark comparator for the noninferiority of other ritonavir-boosted PI regimens. Although generally well tolerated, lopinavir/ritonavir is associated with generally manageable adverse gastrointestinal side effects and hypertriglyceridaemia and hypercholesterolaemia, which may require coadministration of lipid-lowering agents to reduce the risk of coronary heart disease. Lopinavir/ritonavir, in combination with other ART agents, is a well established and cost-effective treatment for both ART-naive and -experienced patients with HIV-1 infection and, with successful management of adverse events, continues to have a role as an effective component of ART regimens for the control of HIV-1 infection.

Dexlansoprazole modified release: in erosive oesophagitis and non-erosive reflux disease.

Dexlansoprazole modified release (dexlansoprazole MR) is an orally administered delayed-release formulation of the R-enantiomer of the proton pump inhibitor lansoprazole that is effective in improving the healing of all grades of erosive oesophagitis, maintaining the healing of erosive oesophagitis and in the treatment of symptomatic non-erosive reflux disease (NERD). In two large, identical, 8-week, randomized, double-blind, multicentre phase III trials, dexlansoprazole MR 60 mg once daily achieved complete healing in >or=92% of patients with all grades of erosive oesophagitis (primary endpoint) and was noninferior to lansoprazole 30 mg once daily using life-table analysis. Moreover, in a randomized, double-blind, multicentre phase III trial in patients with healed erosive oesophagitis, dexlansoprazole MR 30 mg once daily was significantly more effective than placebo in maintaining healing following 6 months' treatment (primary endpoint). In addition, the proportion of 24-hour heartburn-free days (primary endpoint) was significantly greater in recipients of dexlansoprazole MR 30 mg once daily than in recipients of placebo following 4 weeks' treatment in a large, randomized, double-blind, multicentre phase III trial in patients with NERD. Dexlansoprazole MR 30 or 60 mg once daily was generally well tolerated in a pooled analysis of clinical trials of up to 12 months' duration.