Current Drug Safety - Volume 13, Issue 1, 2018

Background: There are many contradictions about pregnancy and fetal/neonatal outcomes after topical use of timolol alone or timolol in combination with other antiglaucoma medications. Methods: Seventy-five pregnant women exposed to antiglaucoma medications were followed prospectively by phone interviews. 27 women used timolol as monotherapy, 48 women used timolol as a part of multidrug therapy. We selected a control group of 187 healthy pregnant women. Results: Topical use of timolol alone or timolol in combination with other antiglaucoma medications does not influence pregnancy or fetal/neonatal outcomes. Conclusion: Beta-blocker is the first choice treatment for glaucoma in pregnancy but, when necessary, multidrug therapy should not to be excluded.

Introduction: Due to the chaos in the legislation in the Middle East, male enhancement nutraceuticals may be sold without any registration or evaluation. These products need to be evaluated with respect to safety and efficacy. Furthermore, cultural and social considerations in the Middle East prevent the use of international evaluations schemes for erectile dysfunction. Aim: Evaluating the safety and efficacy parameters of generic and nutraceutical products for erectile dysfunction in the Middle East through a custom-designed, representable and simple system tailored to the regional culture. Methods: 74 healthy male volunteers were enrolled into a comparative, simple randomized, single dose, double blind, and crossover clinical study incorporated with a tailored-designed questionnaire. Safety assessment included laboratory analysis for liver functions and measuring blood pressure. Main Outcome Measures: Subjective data regarding safety and efficacy were assessed from the validated questionnaire. Blood pressure was measured. Blood samples were collected to assess the drug/adulterants concentration and liver and kidney functions. Results: All tested nutraceuticals showed undeclared Sildenafil citrate in patients. Questionnaire results showed high inter-patient variability with respect to efficacy and comparable safety profile compared to Viagra®. Conclusion: The validated tailored-designed questionnaire effectively assessed the efficacy and safety of male enhancement products. The male enhancement nutraceuticals, sold in Egypt, claimed to be 100% natural are adulterated and of questionable safety profile.

Background: Pharmacovigilance is the science that plays an essential role in the reduction of ADRs which helps in predicting unwanted effects of drugs in community. Studying adverse drug reaction is an important arm of patient care. It aims at making the safe use of medicines for the treatment or prevention of disease. Objectives: To assess knowledge, Practice and attitudes toward pharmacovigilance and adverse drug reactions reporting process among Health Care Providers in Dammam, KSA. Methods: This was a cross-sectional and questionnaire-based study involving health care providers working in different hospitals. 160 questionnaires were distributed to the respondents (25 doctors, 65 nurses, 50 pharmacists and 25 other health care provides). Participants were selected randomly and those not willing to participate were excluded from the study. Chi-square test was used for the calculation of P-Value. Results: 135 participants responded to the questionnaire, while 160 participants were recruited for the study. The majority (n= 99, 73.33%, p=0.007) had no idea about national pharmacovigilance centers of KSA. The standard SFDA adverse drug reaction form was only known to 38.51 %, p=0.028 and only 38.51 %, p=0.002 were aware about electronic reporting of ADR. Only 34 %, p =0.002 of the respondents had ever reported an adverse drug reactions, 76.29 %, p=0.041 have not attended any training on ADR reporting and 86.66%, p=0.045 participants have no idea about impact of ADR reporting. Conclusion: The knowledge and attitude to ADR reporting was inadequate, our study has shown that the actual practice of ADR reporting is unsatisfactory. This indicates that there is a need to create an awareness of the importance of ADR reporting through CME/training of ADR reporting among healthcare providers.

Background: Data have pointed at an impaired fracture healing with fluoroquinolones and thus potentially a decreased bone biomechanical competence. Objectives: To study fracture risk associated with antibiotics. Methods: It is a case control study. There were 124,655 fracture cases and 373,962 age and gender matched controls. The main exposure was use of various groups of antibiotics. Confounder control was performed for social variables, contacts to hospitals and general practitioners, alcoholism and a number of other variables. Results: An increased risk of any fracture (OR =1.45, 95% CI: 1.42 -1.49), hip (1.46, 95% CI: 1.35- 1.58), forearm (1.67, 95% CI: 1.55 -1.80), and spine fractures (1.38, 95% CI: 1.18-1.60) was seen with the use of dicloxacillin and flucloxacillin. There was a dose response relationship for overall risk of fractures, hip, and forearm fractures but not for spine fractures with dicloxacillin and flucloxacillin. None of the other groups of antibiotics against bacteria, tuberculosis, virus, and fungi were systematically associated with any major change in the risk of fractures. Conclusion: Dicloxacillin and flucloxacillin seem associated with an increased risk of fractures. The cause for this increase has to be determined but may be related to their use against infections of the bone, the increase thus rather being due to the underlying disease than the drug. Other types of antibiotics especially the fluoroquinolones were not systematically associated with an increased risk of fractures.

Background: Vaccination is a widespread strategy to protect women and their children during fetal development. However, there is a lack of knowledge about potential effects of H1N1 vaccination on concentration of cytokines that are important to mother's central nervous system functions and fetal neurodevelopment. Objective: The main purpose of the present study was to evaluate such interaction. The specific goals were to study the effects of vaccination against the H1N1 virus on plasma levels of the Brain Derived Neurotrophic Factor(BDNF), Tumor Necrosis Factor-α (TNF-α) and TNF-α Receptors 1 and 2 (sTNFR1; sTNFR2), in different periods of gestation. Methods: Data were obtained during the period of 6 months in 2010, from a sample of 94 pregnant women who were using the health care service of Conceição do Mato Dentro, a rural area in the state of Minas Gerais, Brazil. Seventeen women were in the first trimester of pregnancy, forty were in the second trimester and 37 were in the third trimester. Each of these groups was divided into two subgroups as follows: immunized against the H1N1 virus (I) and non-immunized (NI). Plasma concentrations of BDNF, TNF-α, sTNFR1 and sTNFR2 were measured using the sandwich ELISA. Results: There was no difference in cytokine or neurotrophic factor levels evaluated between groups I and NI in any trimesters. Conclusion: These results show that the recommendation of vaccination against the H1N1 virus for all pregnant women as a public health measure could be considered safe, regarding aspects related to the role played by neurotrophin and cytokine, such as those of CNS development and immunological functions.

Background: Selective agents able to locate and identify unique targets represent a crucial aspect of modern pharmacology. The exclusive location of Sodium-Glucose co-Transporter-2 (SGLUT2) on kidneys prompt companies to develop SGLT2 inhibitors that today are the latest class of drugs for diabetes treatment. In particular, canagliflozin blocks the re-absorption of glucose in the kidney lowering blood glucose levels by increasing glucose excretion. Case Description: We report a 61-year old woman who developed an intense and severe pruritus during the treatment with canagliflozin. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce pruritus. The discontinuation of canagliflozin and the treatment with pioglitazone/metformin fixed combination induced a remission of pruritus. Conclusion: This case emphasizes the need to consider pruritus as a differential diagnosis during the treatment with canagliflozin.

Background: We report a case of 25 years old male patient with antitubercular drugs induced exanthematous reaction and hepatotoxicity that was complicated by levofloxacin induced toxic epidermal necrolysis. The patient was allergic to ciprofloxacin and ofloxacin. Cross reactivity between ciprofloxacin and levofloxacin might be responsible for causing this reaction. Conclusion: Issues of cross sensitivity should be kept in mind and the same class of drugs should strictly be avoided to prevent such complications.

Background: Case report, in a patient with a history of diabetes and hypertension, treated with metformin, gliclazide, enalapril + hydrochlorothiazide, amlodipine, aspirin and diazepam, recently medicated for a gouty crisis with colchicine and clonixin without improvement. Believing it could help in the treatment of gouty crisis symptoms he took about 1.5 L of artichoke infusion (Cynara cardunculus). He felt better and did agriculture work but developed a distal muscle pain, severe anemia, standard biochemical liver cholestasis, increase of alkaline phosphatase and marked increase of inflammatory parameters (hyperleucocytosis) and enters in the emergency department at the hospital. Objective: Evaluation of the cause of complaints and laboratory abnormalities and the involvement of artichoke infusion. Results: The prominence of the inflammatory parameters was ruled out because of exhaustive autoimmune, infectious or para-neoplastic syndrome (blood cultures, serology, diagnostic imaging, bone marrow and bone biopsy, muscle biopsy and nerve, abdominal angiography) were carried out showing normal results. The evaluation pointed out that the concomitant intake of artichoke infusion may have been involved in the framework developed, since the drugs which were being administered to/by the patient have a metabolism mainly mediated by CYP450 3A4 and 2C9 that could be compromised when these isoenzymes are inhibited by phenolic and flavonoid compounds from plants. Colchicine was one of the last drugs took that have as side effects most of the symptoms felt by patient including diarrhea and anemia. Conclusion: The spontaneous and complete recovery of the patient and the negativity of research looking for other causes, conduce to a strong possibility of the interaction between artichoke and the drugs in the clinical presentation of this case.

Introduction: Self-medication behavior appears to be a commonplace; and when it is ignorant it may prove dangerous. On the other hand, dispensing errors and consequent adverse outcomes, though not too uncommon, are seldom reported. We report here a case of methotrexateinduced acute vesico-bullous eruptions in a patient of psoriasis who indulged in self-medication and was wrongfully dispensed higher doses of methotrexate. Case Description: A 50-year-old man was diagnosed with psoriasis two years back and advised tablet methotrexate 20 mg once weekly and folic acid supplementation. He experienced symptoms remission after 8 weeks of treatment and preferred to discontinue the medication. As the psoriatic lesions reappeared four weeks ago, he attended a retail pharmacy for refill of the two-year old prescription. He was obliged by the man in the counter who wrongfully dispensed the medicine and the patient consumed methotrexate 10 mg twice daily. On the 20th days, the patient experienced erythematous, vesico-bullous lesions spread all over the body including both limbs and scalp, with oral mucosal involvement without any history of fever, and with mildly deranged liver function, and presented to the dermatology OPD of a tertiary hospital. He was admitted and treated with injection glucocorticoid and leucovorin. He responded well and completely recovered in a week. A ‘probable’ causality was adjudged for this serious adverse event by both WHO-UMC scale and Naranjo's algorithm. The reaction was moderately severe (Hartwig's scale) and it was definitively preventable (modified Schumock-Thornton scale). Conclusion: This case report highlights the hazard of uninformed Self-medication and irresponsible dispensing behavior resulting in serious drug-related injury.

Background: Hyperammonemia is an infrequent adverse drug reaction (ADR) of chemotherapy. A few cases of 5-fluorouracil (5-FU) related hyperammonemia have been reported. However, hyperammonemia induced by capecitabine, an oral prodrug of 5-FU, has not been reported till date. Case Report: A patient with colon cancer was treated with CapeOx (oxaliplatin 200mg, day 1; capecitabine 1.5g bid, days 1-14). On the fifth day of first cycle chemotherapy, she developed hyperammonemia (245 μmol/L) and psychiatric symptoms. The serum 5-FU level (3.2μg/L) was lower than normal. When the patient recovered with drug treatment, capecitabine was restarted at a lower dose (1g bid). Hyperammonemia (98μmol/L) and psychiatric symptoms reappeared after three days. Serum 5-FU remained at a low level (4.6μg/L). This case highlighted the possibility of hyperammonemia induced by capecitabine. Case reports such as these would make physicians more aware of rare ADR and what to be done in such case.

Background: Only few cases have been reported with cardiovascular side effects, especially congestive heart failure (HF), of intraconazole therapy after black box warning by US-FDA (2001). It is unknown which category of patients should avoid this important antifungal treatment. Case Report: A middle-aged man having past history of treated pulmonary tuberculosis and obstructive uropathy presented with 2-weeks of progressive cough with scanty purulent sputum and breathlessness without any fever, chest pain, or pedal edema. Chest examination demonstrated bilateral crackles in upper thorax. Kidney function tests were deranged. Imagings revealed both upper lobe fibrosis with an aspergilloma. He received tablet itraconazole (200mg BD) and on 3rd day, he developed signs and symptoms of congestive HF. With diuretics and stopping of itraconazole, he recovered. With WHO-UMC criteria, probable drug-induced HF was diagnosed. Hence, this case reaffirms a causal relationship between itraconazole and HF. Although previous case studies have characterised cardiac risk factors as relative contraindication to the use itraconazole; this case outlines a caution (or relative contraindication) for systemic use of the drug with non-cardiac risk factors like lungs pathology in form of old koch's fibrotic chest and/or chronic kidney disease; where posaconazole may be a better treatment of choice considering availability and cost issue.

Background: Two female breast cancer patients developed epiphora after administration of cyclophosphamide and/or anthracyclines based 2-day chemotherapy regimen. An ophthalmologist was consulted and no apparent cause was found. Case Description: Patients were managed by ciprofloxacin eye drops. Chemotherapy induced ocular complications are not uncommon, but under reported. Although epiphora is a mild reaction, if severe however, it can interfere with daily activities. Patients having chemotherapy induced ocular toxicity should go for ophthalmic examination to pick up ocular adverse effects of anticancer drugs and treat them at an early stage.

Background: Misoprostol is a synthetic analog of prostaglandin-E1 and it is the most widely used drug for the medical management of incomplete abortion. Acute Coronary Syndrome (ACS) rarely occurs in perimenopausal women, in addition, its presentation is atypical, so the disease is not always recognized. Case Report: We describe a case of 39-year-old woman with no major underlying cardiovascular risk factors, who developed an episode of ACS following the administration of two doses of misoprostol. After the discontinuation of misoprostol treatment, there was a complete resolution of patient's symptoms. The case draws attention to a rare side effect of a commonly used drug and alerts the clinicians to be cautious in those patients having baseline risk factors which make the patient more susceptible to such serious adverse drug effect.

Objective: Dolutegravir (DTG), a highly effective second-generation HIV integrase inhibitor with high genetic barrier to resistance, has shown excellent tolerability and safety profiles in clinical trials. However, some patients may experience neurological or psychiatric adverse effects leading to DTG discontinuation. Case Report: This report describes a case of 29-year-old woman who developed neurological adverse events after starting the DTG-based antiretroviral therapy. Serum DTG concentrations were supratherapeutic which has required a dosing interval adjustment. The findings of this case report suggest that Therapeutic Drug Monitoring might be useful in individuals expressing unusual DTG pharmacokinetics.