Journal of Pharmacy Technology

To review salvage options for Helicobacter pylori eradication regimens during a tetracycline backorder for patients with triple-therapy failure.

A search of PubMed (1980-June 2012) was conducted using a combination of the terms H. pylori or Helicobacter pylori, salvage therapy, and eradication or treatment as text word searches.

Clinical trials and meta-analyses published in English were included. A manual review of the bibliographies of available literature was conducted and relevant articles were reviewed for inclusion.

Treatment of H. pylori consists of a triple-drug regimen that includes a proton pump inhibitor (PPI), amoxicillin or metronidazole, and clarithromycin. Failure with this therapy is becoming increasingly common due to macrolide resistance. Upon failure with this regimen, it is recommended that a quadruple regimen with bismuth subsalicylate, metronidazole, tetracycline, and a histamine₂ receptor antagonist or a PPI be used. Recent backorders by the 2 manufacturers for tetracycline restrict the use of this regimen. Options that can be considered include minocycline or doxycycline in place of tetracycline, levofloxacin- or moxifloxacin-based regimens, a tinidazole-based regimen, or a rifabutin-based regimen. This article includes a review of 1 study each of minocycline and doxycycline, 5 levofloxacin studies (including meta-analyses), 2 moxifloxacin studies, 1 rifabutin study, and 1 tinidazole study. There are limited data with other tetracyclines; however, given the resistance to quinolones in some areas and possible drug interactions and adverse effects from rifabutin, minocycline or doxycycline regimens may be a better second-line regimen option.

Given the current tetracycline shortage, minocycline and doxycycline are options to be considered in patients with a macrolide-based treatment failure. Fluoroquinolones may be an option for patients who have not received these drugs for other indications in the recent past or in areas where resistance is low.

To report a case of peripheral and autonomic neuropathy following one cycle of bortezomib in a patient with newly diagnosed multiple myeloma.

A 75-year-old male who was highly functional prior to therapy rapidly became bed-bound from hypotension, syncope, and peripheral neuropathy after initiating bortezomib. Orthostatic hypotension and syncope persisted despite exclusion of infection and endocrine derangements and his receiving adequate intravenous hydration. Five weeks after this single cycle, the patient had a complete treatment response, including undetectable M-spike, improved anemia, and return to baseline renal function. An objective causality assessment revealed that an adverse drug event was probable.

Although neurotoxicity is an adverse effect of bortezomib, a MEDLINE search revealed little evidence on autonomic neuropathy, such as orthostatic hypotension and syncope. Also unique is the patient's complete treatment response following this single cycle. One explanation for the toxicities and dramatic treatment response is increased bortezomib exposure due to decreased drug metabolism. Both drug interactions and genetic polymorphisms can reduce bortezomib metabolism via effects on cytochrome P450 enzymes. Our patient was concomitantly taking 4 CYP inhibitors; amiodarone and omeprazole were longstanding, and ciprofloxacin and fluconazole were recently initiated prior to chemotherapy. Of these, fluconazole inhibits CYP2C9, 2C19, and 3A4; amiodarone inhibits CYP3A4, 1A1, 1A2, 2B6, and 2D6; ciprofloxacin inhibits CYP1A2 and 3A4; and omeprazole inhibits CYP1A2, 2C19, 2C9, 2D6, and 3A4. Similarly, genetic variables affect CYP enzymes. Genetic testing can predict response to bortezomib therapy, but pretherapy testing is not standard practice due to availability and cost, as in our patient's case.

CYP-inhibiting drugs and many genetic polymorphisms can reduce bortezomib metabolism and increase serum concentrations of the drug, but guidelines on drug-drug interactions, monitoring, and genetic testing prior to bortezomib toxicity are needed.

To report on a patient who required increased dosages of warfarin to achieve therapeutic anticoagulation while taking dicloxacillin.

A 60-year-old woman was hospitalized for an infected lymphocele and cellulitis. Based on microbiology results, dicloxacillin 500 mg by mouth 4 times daily was initiated to complete 14 days of treatment. Concurrently, a deep vein thrombosis was diagnosed by computed tomography angiography. Enoxaparin 100 mg subcutaneously twice daily and warfarin 5 mg by mouth daily were initiated with an international normalized ratio (INR) goal of 2–3. The patient had a history of a supratherapeutic INR while on warfarin 5 mg daily. Throughout the 20-day hospitalization, her warfarin dose was steadily increased in an attempt to achieve a therapeutic INR. Required doses ranged from 7.5 to 15 mg daily. Two days after discontinuation of dicloxacillin and with administration of a 15-mg warfarin boost, the INR was therapeutic at 2.3. Enoxaparin was discontinued and the patient was discharged on warfarin 7.5 mg daily. Upon clinic follow-up 5 days after discharge, the INR was supratherapeutic at 3.3 and the warfarin dose was decreased. The patient was then lost to follow-up.

This interaction between warfarin and dicloxacillin has been described in the literature; however, the mechanism responsible remains unknown. In all cases reported, increased warfarin requirements appeared after several days of dicloxacillin therapy and slowly disappeared after dicloxacillin discontinuation. This case differs from previously reported cases because it demonstrates warfarin resistance associated with dicloxacillin and a subsequent new initiation of warfarin therapy. The Naranjo probability scale and the Horn Drug Interaction Probability Scale both rate this interaction as probable.

Patients taking dicloxacillin who are initiated on warfarin may require a longer duration of concurrent low-molecular-weight heparin therapy, as well as higher doses of warfarin, and may take longer to achieve a therapeutic INR.

To report a case of paroxysmal atrial fibrillation in a patient who was receiving a chemotherapy regimen including docetaxel plus cyclophosphamide (TC).

A 67-year-old woman was receiving TC therapy for stage IIB breast cancer. She developed symptomatic paroxysmal atrial fibrillation following chemotherapy administration. The patient presented with tachycardia-palpitations, a shaking sensation inside her body, shortness of breath, and tightness in her chest that did not radiate. Propafenone treatment was replaced with sotalol. Cycle 2 of chemotherapy was administered and symptoms of atrial fibrillation returned. Sotalol was switched to dronedarone monotherapy and the symptoms resolved.

Based on the Naranjo probability scale, chemotherapy was the probable cause of the patient's episodes of paroxysmal atrial fibrillation.

As single agents, taxanes have minimal cardiac toxicity, although cardiac toxicity may be higher with precipitating factors. Clinicians caring for patients receiving taxane chemotherapy should be aware of the potential for docetaxel-induced paroxysmal atrial fibrillation.

To report a case of spontaneous bruising with concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) and citalopram.

A 34-year-old white woman with a history of chronic thrombocytopenia (baseline platelet count 120–130 × 10³/μL) presented to the emergency department (ED) after noticing an increase in bruising on her upper and lower extremities. When the patient was interviewed, it was found that her dose of citalopram had been recently increased from 20 to 40 mg/day and she had started ibuprofen (dose unknown) on her own to manage rib pain approximately 1 month after the citalopram dosage increase. The patient was advised to discontinue ibuprofen and was discharged. Shortly thereafter, she was started on oxaprozin 600 mg twice daily for management of trochanteric bursitis. She returned to the ED stating that bruising occurred 1 week after she was given oxaprozin. At this visit, the patient was told to discontinue oxaprozin and naproxen 440 mg twice daily was prescribed. One week later, the patient again returned to the ED with complaints of spontaneous bruising. At this point citalopram and naproxen were discontinued and she was started on acetaminophen (dose not documented) and buspirone 10 mg twice daily. No other episodes of ecchymosis have occurred in the 8 months since this change to her drug regimen.

Medications that increase the risk of bleeding should be carefully administered in patients who have a low platelet count. This patient experienced bruising when her dose of citalopram was increased and an increase in bruising when she combined an NSAID with citalopram. Selective serotonin reuptake inhibitors (SSRIs) may increase antiplatelet activity of NSAIDs and could therefore increase the risk of bruising. Use of the Horn Drug Interaction Probability Scale indicated a possible interaction with concomitant use of NSAIDs and citalopram.

Patients who experience NSAID- and/or SSRI-related bruising should consult their providers and alternative treatments should be considered.

To report a case of metformin-associated exacerbation of chronic pancreatitis and examine this possible drug-disease interaction.

A 59-year-old woman with chronic pancreatitis (CP) experienced a severe exacerbation of her characteristic chronic abdominal pain 3 weeks after initiation and titration of metformin therapy; the exacerbation resolved upon discontinuation of metformin. The patient presented to the emergency department experiencing nausea and severe right upper quadrant abdominal pain with radiation to the right flank. Persistent abdominal pain, which had been a primary feature of CP, was previously mild and easily controlled with oral analgesics. Laboratory studies ruled out acute pancreatitis and were significant only for elevated glucose (168 mg/dL). Subsequently, she was given intravenous pain and nausea medications and discharged to home. The pain and nausea shortly returned and continued for 3 more days, at which point she telephoned her gastroenterologist, who advised that she discontinue metformin because of possible adverse reaction. Within a few days of discontinuing metformin, the nausea resolved and abdominal pain gradually returned to baseline level.

Metformin is not generally known to cause or exacerbate pancreatitis, although cases of acute pancreatitis associated with metformin therapy have been reported in the literature. No cases involving chronic pancreatitis have been reported. Consequently, metformin's prescribing guidelines do not contain precautions or contraindications for patients with chronic pancreatitis. Use of the Naranjo probability scale for assessment of this case revealed that the adverse drug effect was possible, reflecting the symptomatic resolution upon discontinuation while accounting for the lack of causative certainty, previous conclusive case reports, as well as the presence of possible nondrug causes.

To our knowledge, this is the first case describing metformin-associated exacerbation of chronic pancreatitis. Although this occurrence may be rare, cautionary consideration, education, and monitoring should accompany initiation of metformin therapy in select patients with chronic pancreatitis.

To assess the safety and efficacy of FDA-approved and in-development antiobesity agents.

Literature was accessed through MEDLINE (1950-current) and EMBASE using the terms antiobesity agent, diethylpropion, phentermine, orlistat, topiramate, lorcaserin, bupropion, and naltrexone. In addition, reference citations from publications identified were reviewed. Files related to FDA expert panel hearings were retrieved from the FDA website.

Randomized double-blind trials assessing the efficacy and safety of antiobesity agents compared with placebo in the treatment of overweight and obese adults were reviewed. Only English-language or English-translated literature was reviewed. Medications were selected based on FDA approval status.

Ten double-blind clinical trials were reviewed. There are currently 5 FDA-approved antiobesity agents and 1 agent recently rejected by the FDA. Study results for all agents showed statistically significant weight loss compared with placebo, but with varying adverse effects. The combination of phentermine and topiramate is the most efficacious antiobesity agent approved by the FDA. However, this combination has various neurologic, cardiovascular, and teratogenic safety risks that may limit its use. Based on its safety profile, orlistat is the preferred antiobesity medication, despite the lesser extent to which it induces weight loss versus newer agents. The incidence of unwanted gastrointestinal adverse effects limits its use.

Despite a glaring medical need for options to treat obesity, available medications are limited. No current drug option is ideal; each has either safety risks or efficacy concerns. Safe agents that meet FDA efficacy standards are needed to help treat the obesity epidemic.