Current Drug Safety - Volume 11, Issue 3, 2016

Opioids have been the mainstay for management of acute postoperative pain for several decades. Extensive use, however, has been associated with multiple side effects. Multimodal approaches that incorporate nonopioid medications and techniques have been observed to achieve optimum pain control whilst decreasing side effects. Such strategies are particularly important to consider for opioid-dependent and tolerant patients with various comorbidities undergoing different types of surgery. This review assesses recent data on nonopioid analgesics for postoperative pain control, highlighting evidence of their safety profiles in contemporary pain management.

In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. Objective: To evaluate the effect of tramadol on QT-interval in the clinical setting. Research Design and Methods: Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. Results: 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean ± SD (range), showed QTcB 372±32 (305 to 433), QTcFri 356±37 (281 to 429), QTcFra 363±33 (299 to 429), QTcH 362±30 (304 to 427), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. Conclusion: Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.

Background: Forty-seven cases (38 men and 9 women) of pulmonary toxicity caused by oxaliplatin have previously been published, but the issue has not been investigated in a prospective setting. Our purpose was to assess how oxaliplatin affects the pulmonary function in colorectal cancer patients during adjuvant treatment. Material and Methods: Forty patients (median age 57.5 years, range 33-74) radically resected for colorectal cancer, underwent three pulmonary function tests during post-surgery adjuvant treatment with oxaliplatin. Results: Mean±sd haemoglobin corrected diffusion capacity (DLCOc) in the entire patient cohort were 7.65±2.24 at baseline, 7.11±2.11 during and 7.12±1.99 three months after oxaliplatin treatment (p=0.0002). The decrease was similar in men (n=22, p=0.02) and women (n=18, p=0.01), but most prominent in smokers (n=23, p=0.0005) and in patients exposed to occupational dust (n=21, p=0.0009). Besides a small decrease in the FEV1/FVC ratio (p=0.03), all other pulmonary parameters remained constant and no clinical signs of pulmonary failure were observed during the study period. Conclusion: A decline in DLCOc was detected in a majority of the examined patients, but none reported any clinical symptoms of pulmonary distress. The subtle decrease in DLCOc does not appear to be an isolated predictor of PT. Our data suggest that smoking and dust exposure might aggravate the effect of oxaliplatin on DLCOc. Routine pulmonary function test in patients treated with oxaliplatin is not recommended, but it is important to be aware of the early signs of pulmonary toxicity.

Introduction: Multiple pregnancies are a recognized adverse effect of assisted reproductive technologies; nevertheless, there is no consensus on the incremental risk associated with the ovarian stimulation (OS) used alone and intrauterine insemination (IUI). The relationship between OS and IUI and the risk of major congenital malformations (MCM) is unclear. Objective: To summarise the literature and evaluate the risk of multiple pregnancy and MCM associated with OS used alone and IUI used with or without OS compared to natural conception (spontaneously conceived infants without any type of fertility treatments). Methods: We carried out a systematic review to identify published papers between 1966 and 2014 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. We included observational studies and randomized clinical trials related to the risk of multiple pregnancies and MCM conceived following OS alone or IUI compared to natural conception (spontaneously conceived infants without any fertility treatments). The quality of the included studies was evaluated using The Cochrane Collaboration’s tool for assessing risk of bias for RCTs and the Newcastle–Ottawa Scale for observational studies. Results: There were 63 studies included in this review. Our systematic review suggests that the use of any OS alone was associated with an increased risk of multiple pregnancy compared to natural conception (pooled RR 8.80, 95% CI 5.09- 15.20; p= 0.000; 9 studies). Similar increases in the risk of multiple pregnancies were observed following clomiphene citrate used without assisted reproductive technologies. Compared to natural conception, the use of IUI with or without OS was associated with an increased risk of multiple pregnancy (pooled RR 9.73, 95% CI 7.52 -12.60; p= 0.000; 6 studies). Compared to natural conception, the use of any OS alone was associated with an increased risk of any MCM (RR pooled 1.18, 95%CI 1.03-1.36; 11 studies), major musculoskeletal malformations (pooled RR 1.48, 95%CI 1.21-1.81; 7 studies), and malformations of the nervous system (pooled RR 1.73, 95%CI 1.15-2.61; 6 studies). Compared to natural conception, the use of IUI was associated with an increased risk of any MCM (pooled RR 1.23, 95%CI 1.10-1.37; 10 studies), major urogenital (pooled RR 1.52, 95%CI 1.04-2.22; 7 studies), and musculoskeletal malformations (pooled RR 1.54, 95%CI 1.20-1.98; 7 studies). The overall quality of the included studies was acceptable. Conclusions: The increased risk of multiple pregnancy and certain types of MCM associated with the use of less invasive fertility treatments, such as OS and IUI, found in this review, highlights the importance of the practice framing. Heterogeneity in OS protocols, the combination with other fertility agents, the limited number of studies and the methodological quality differences reduce our ability to draw conclusions on specific treatment. More observational studies, assessing the risk of multiple pregnancy or MCM, as a primary outcome, using standardized methodologies, in larger and better clinically defined populations are needed.

Clozapine is an antipsychotic drug recommended for resistant schizophrenia, but its widespread use is limited by adverse effects. Sialorrhea is a common and troublesome adverse effect seen with clozapine which leads to poor compliance. Several treatment strategies are advocated, no single treatment is considered superior. Amitriptyline, a tricyclic antidepressant, has been found to be useful for clozapine-associated sialorrhea at 87–100 mg per day. We report the effect of very low dose amitriptyline (10 mg per day) in a patient with clozapine-associated sialorrhea. There was rapid and complete resolution of sialorrhea after three days without any emergent adverse effect.

Introduction: Nutraceutical is a term applied for a plethora of products ranging from isolated nutrients, herbal products to dietary supplements and recently, the interest for a nutraceutical approach to lipid and metabolic disorders is growing. Patients with metabolic conditions seem to appreciate a therapeutic management that does not involve drug treatment, particularly for the side effects due to statins, a class of drug used for lipid disorders. Statins directly induce skeletal muscle injury and in the elderly patients, under polytherapy treatments, this risk relies to an increase in adverse drug reactions due to drug interactions. Case Description: Herein we report a 70-year-old woman under polytherapy who developed rhabdomyolysis after starting the administration of a dietary supplement containing monacolin K. Using the Drug Interaction Probability Scale, we postulated that rhabdomyolysis was possibly related to a drug interaction between sertraline, rosuvastatin and monacolin K. These treatments were discontinued leading to a remission of both clinical symptoms and biochemical parameters. Conclusion: This case report highlights how pharmacological treatment must be periodically reassessed, since elderly people could take drugs by themselves when they donot need.

Zoledronate is a Nitrogen containing bisphosphonate (NBP) used in many conditions like osteoporosis, Paget’s disease and hypercalcemia of malignancy. Unlike oral bisphosphonates, Zoledronate is not seen to be associated with gastroesophageal side effects but the drug is not free of certain rare but life threatening adverse effects like hypocalcemia and renal deterioration. Majority of cases of hypocalcemia with Zoledronate are seen in patients with underlying malignancy and are asymptomatic. Here we present a case of severe symptomatic hypocalcemia along with hypophosphatemia following zoledronate administration in an elderly male with a history of osteoporotic fracture.

Intravitreal triamcinolone and bevacizumab are emerging treatment modalities for the patients of macular oedema; however, they are known to raise intraocular pressure. A 61 year old diabetic male patient developed glaucoma after administration of triamcinolone acetonide and bevacizumab intravitreally for treatment of macular oedema. His intraocular pressure was raised up to about 42 mm Hg. Such high and sustained rise in intraocular pressure may lead to vision loss by damaging the optic nerve. The patient was managed by local as well as systematic therapy and was recovered after 1 month from the occurrence of an event. Intraocular pressure should be monitored in patients receiving intravitreal triamcinolone and bevacizumab. Risk benefit analysis must be done before using IVTA and IVB in patients with diabetic macular oedema.

A 28 year old male patient, known case of pemphigus vulgaris was on dexamethasone pulse therapy. Total 7 pulses were given after that he developed avascular necrosis of head of femur on both sides, which was confirmed by digital X- ray and MRI. Avascular necrosis is a disabling and progressive condition in young patients gradually leads to femoral head collapse and eventual total hip arthroplasty. As per WHO-UMC causality assessment criteria, the association between reaction and drug was possible, Naranjo’s score was 7. According to Modified Schumock and Thornton’s criteria, this reaction was not preventable. The Modified Hartwig and Siegel’s scale showed that the reaction was severe (level 6). Here we present a case where the use of steroid for pemphigus vulgaris resulting in the development of bilateral avascular necrosis of head of femur.