Ofloxacin-ornidazole fixed-dose combination medication-induced pancreatitis with positive rechallenge

A 36-year-old Asian Indian male came to the triage room of our hospital with recent-onset abdominal pain. The pain was largely centered in the upper middle quadrant, which was piercing type, 7/10 on the severity scale, radiating to back, worsening with any move, and improving with respite. He disclaimed being suffering from any other illness except generalized anxiety disorder on the current illness history. His medical history was only substantial for hypovitaminosis D, for which he completed the vitamin D supplementation treatment course 1 month back. There was no positive surgical history. He was not consuming any drugs except amitriptyline for anxiety disorder for the past 8 years. The only medicine patient consumed preceding pain onset was ofloxacin-ornidazole FDC (200 mg ofloxacin and 500 mg ornidazole containing) tablet. The abdominal pain started 2 h after oral intake of ofloxacin-ornidazole FDC tablet obtained without prescription, reaching sufficient severity by 12 h requiring medical consultation in an emergency room. On further questioning, the patient recalled that 3 years ago he had similar abdominal pain that developed after taking ofloxacin-ornidazole FDC (with the different brand name) and had to see a doctor in an emergency. He was diagnosed as acute pancreatitis [Table 1]. The pain of the past episode responded within a few minutes to hours to painkiller injection with a reduction in the food intake on the clinician’s advice. The patient is nonalcoholic; has never smoked or taken any recreational drugs. On evaluation, his vitals were stable. Tenderness was elicited in epigastrium on palpation without any guarding or the rigidity. Biochemical examination showed a raised concentration of lipase 635 units/L and amylase 377 units/L in the serum. CT examination of the abdomen was noteworthy for grade C acute pancreatitis (peripancreatic and perirenal fat stranding) with no collection formation [Figure 1]. Ultrasound examination of the abdomen ruled out the possibility of gallstone [Table 1]. The patient had normal triglycerides and calcium levels had no present or history of sepsis, injury, malignancy, or scorpion bite.

Ofloxacin

Taking ofloxacin increases the risk that you will develop tendinitis (swelling of a fibrous tissue that connects a bone to a muscle) or have a tendon rupture (tearing of a fibrous tissue that connects a bone to a muscle) during your treatment or for up to several months afterward. These problems may affect tendons in your shoulder, your hand, the back of your ankle, or in other parts of your body. Tendinitis or tendon rupture may happen to people of any age, but the risk is highest in people over 60 years of age. Tell your doctor if you have or have ever had a kidney, heart, or lung transplant; kidney disease; a joint or tendon disorder such as rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function); or if you participate in regular physical activity. Tell your doctor and pharmacist if you are taking oral or injectable steroids such as dexamethasone , methylprednisolone (Medrol), or prednisone (Rayos). If you experience any of the following symptoms of tendinitis, stop taking ofloxacin, rest, and call your doctor immediately: pain, swelling, tenderness, stiffness, or difficulty in moving a muscle. If you experience any of the following symptoms of tendon rupture, stop taking ofloxacin and get emergency medical treatment: hearing or feeling a snap or pop in a tendon area, bruising after an injury to a tendon area, or inability to move or bear weight on an affected area.

Taking ofloxacin may cause changes in sensation and nerve damage that may not go away even after you stop taking ofloxacin. This damage may occur soon after you begin taking ofloxacin. Tell your doctor if you have ever had peripheral neuropathy (a type of nerve damage that causes tingling, numbness, and pain in the hands and feet). If you experience any of the following symptoms, stop taking gemifloxacin and call your doctor immediately: numbness, tingling, pain, burning, or weakness in the arms or legs; or a change in your ability to feel light touch, vibrations, pain, heat, or cold.

Taking ofloxacin may affect your brain or nervous system and cause serious side effects. This can occur after the first dose of ofloxacin. Tell your doctor if you have or have ever had seizures, epilepsy, cerebral arteriosclerosis (narrowing of blood vessels in or near the brain that can lead to stroke or ministroke), stroke, changed brain structure, or kidney disease. If you experience any of the following symptoms, stop taking ofloxacin and call your doctor immediately: seizures; tremors; dizziness; lightheadedness; headaches that won’t go away (with or without blurred vision); difficulty falling asleep or staying asleep; nightmares; not trusting others or feeling that others want to hurt you; hallucinations (seeing things or hearing voices that do not exist); thoughts or actions towards hurting or killing yourself; feeling restless, anxious, nervous, depressed, memory problems, or confused, or other changes in your mood or behavior.

Taking ofloxacin may worsen muscle weakness in people with myasthenia gravis (a disorder of the nervous system that causes muscle weakness) and cause severe difficulty breathing or death. Tell your doctor if you have myasthenia gravis. Your doctor may tell you not to take ofloxacin. If you have myasthenia gravis and your doctor tells you that you should take ofloxacin, call your doctor immediately if you experience muscle weakness or difficulty breathing during your treatment.

Talk to your doctor about the risks of taking ofloxacin.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with ofloxacin. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (https://www.fda.gov/Drugs) or check the manufacturer’s website to obtain the Medication Guide.

Why is this medication prescribed?

Ofloxacin is used to treat certain infections including pneumonia, and infections of the skin, bladder, reproductive organs, and prostate (a male reproductive gland). Ofloxacin may also be used to treat bronchitis and urinary tract infections but should not be used for bronchitis and some types of urinary tract infections if other treatments are available. Ofloxacin is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections.

Antibiotics such as ofloxacin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

How should this medicine be used?

Ofloxacin comes as a tablet to take by mouth. It is usually taken with or without food twice a day for 3 days to 6 weeks. The length of treatment depends on the type of infection being treated. Your doctor will tell you how long to take ofloxacin. Take ofloxacin at around the same times every day and try to space your doses 12 hours apart. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ofloxacin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

You should begin to feel better during the first few days of your treatment with ofloxacin. If your symptoms do not improve or if they get worse, call your doctor.

Take ofloxacin until you finish the prescription, even if you feel better. Do not stop taking ofloxacin without talking to your doctor unless you experience certain serious side effects that are listed in the IMPORTANT WARNING and SIDE EFFECT sections. If you stop taking ofloxacin too soon or if you skip doses, your infection may not be completely treated and the bacteria may become resistant to antibiotics.

Other uses for this medicine

Ofloxacin is also sometimes used to treat other types of infection, including Legionnaires’ disease (type of lung infection), certain sexually transmitted diseases, infections of the bones and joints and of the stomach and intestines. Ofloxacin may also be used to treat or prevent anthrax or plague (serious infections that may be spread on purpose as part of a bioterror attack) in people who may have been exposed to the germs that cause these infections in the air. Ofloxacin may also be used to treat or prevent travelers’ diarrhea in certain patients. Talk to your doctor about the risks of using ofloxacin to treat your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before taking ofloxacin,

• tell your doctor and pharmacist if you are allergic or have had a severe reaction to ofloxacin; other quinolone or fluoroquinolone antibiotics such as ciprofloxacin (Cipro), gemifloxacin (Factive), levofloxacin (Levaquin), and moxifloxacin (Avelox); any other medications; or any of the ingredients in ofloxacin tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take while taking ofloxacin. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• if you are taking antacids containing aluminum, calcium, or magnesium (Maalox, Mylanta, Tums, others); or certain medications such as didanosine (Videx) solution; sucralfate (Carafate); or supplements or multivitamins containing iron or zinc, take ofloxacin 2 hours before or 2 hours after you take these medications.
• the following nonprescription products may interact with ofloxacin: cimetidine (Tagamet); nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve). Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking ofloxacin. Do not start any of these medications while taking ofloxacin without discussing with your healthcare provider.
• tell your doctor if you or anyone in your family has or has ever had a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death). Also, tell your doctor if you have or have ever had an irregular or slow heartbeat, a heart attack, an aortic aneurysm (swelling of the large artery that carries blood from the heart to the body), high blood pressure, peripheral vascular disease (poor circulation in the blood vessels), Marfan syndrome (a genetic condition that can affect the heart, eyes, blood vessels and bones), Ehlers-Danlos syndrome (a genetic condition that can affect skin, joints, or blood vessels), or have a low level of potassium or magnesium in your blood. Also tell your doctor if you have or have ever had diabetes or problems with low blood sugar or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking ofloxacin, call your doctor.
• do not drive a car, operate machinery, or participate in activities requiring alertness or coordination until you know how ofloxacin affects you.
• plan to avoid unnecessary or prolonged exposure to sunlight and ultraviolet light (tanning beds and sunlamps) and to wear protective clothing, sunglasses, and sunscreen. Ofloxacin may make your skin sensitive to sunlight or ultraviolet light. If your skin becomes reddened, swollen, or blistered, call your doctor.

What special dietary instructions should I follow?

Make sure you drink plenty of water or other fluids every day while you are taking ofloxacin.

Ofloxacin-ornidazole fixed-dose combination medication-induced pancreatitis with positive rechallenge

Received 2020 Apr 3; Revised 2020 Apr 26; Accepted 2020 May 8; Collection date 2020 Jun.

Copyright: © 2020 Journal of Family Medicine and Primary Care

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

PMCID: PMC7491762 PMID: 32984191

Abstract

Although ofloxacin-ornidazole fixed-dose combination (FDC) is a rampantly used antibiotic combination for mixed-infection diarrhea in India, the adverse drug reaction (ADR) associated with these FDCs remains underreported. Herein, the authors present a case report of a definitive ofloxacin-ornidazole FDC-induced pancreatitis. The nonalcoholic adult male patient showed a sharp piercing epigastric pain flowing to the back, gradually rising in severity, which started after taking ofloxacin-ornidazole FDC tablet over the counter. Serum lipase concentration measured in the emergency room was 635 units per liter (normal range- 13–60 units/L) and serum amylase was 377 units/L (normal range- 30–110 units/L). Ultrasonography and an axial computed tomography of the abdomen confirmed the diagnosis of acute pancreatitis. Ofloxacin-ornidazole FDC tablet was stopped immediately. Past treatment records confirmed accidental rechallenge. In conclusion, this is a first case report of ofloxacin-ornidazole FDC-induced pancreatitis.

Keywords: Adverse event, ofloxacin, ornidazole, pancreatitis, positive rechallenge

Introduction

Drugs account for 1–5% of the total pancreatitis cases, sometimes the third most common after alcohol and gallstones.[1,2] Criteria to conclude the drug as an etiology for pancreatitis includes the following: requirement of temporal association establishment, ruling out the other causes of the disease, symptomatic betterment on dechallenge of the putative drug, and recurrence of symptoms on rechallenge.[3] The US FDA recently issued a warning of dysglycemia with certain fluoroquinolones such as ofloxacin, ciprofloxacin, gemifloxacin, levofloxacin, and moxifloxacin based upon post-marketing reviews in the USA.[4] These drugs penetrate the pancreatic tissues and help in the management of the infectious etiology; however, adverse events such as pancreatitis remain underreported to an extent that there are very few case reports of ciprofloxacin-induced pancreatitis.[5] On a similar note, metronidazole, a nitroimidazole, is known to be associated with the adverse event of pancreatitis. The extent of association between this nitroimidazole-induced pancreatitis rises to eight folds in the presence of other drugs like amoxicillin and proton pump inhibitors, commonly co-prescribed in management of Helicobacter pylori– induced peptic ulcer disease. The congener of same class ornidazole on its own has been infrequently linked to pancreatitis in the literature.[6] Herein, we present the case report where naturally occurring rechallenges at the patient’s end established the ofloxacin-ornidazole fixed-dose combination-induced (FDC-induced) pancreatitis.

Case Report

A 36-year-old Asian Indian male came to the triage room of our hospital with recent-onset abdominal pain. The pain was largely centered in the upper middle quadrant, which was piercing type, 7/10 on the severity scale, radiating to back, worsening with any move, and improving with respite. He disclaimed being suffering from any other illness except generalized anxiety disorder on the current illness history. His medical history was only substantial for hypovitaminosis D, for which he completed the vitamin D supplementation treatment course 1 month back. There was no positive surgical history. He was not consuming any drugs except amitriptyline for anxiety disorder for the past 8 years. The only medicine patient consumed preceding pain onset was ofloxacin-ornidazole FDC (200 mg ofloxacin and 500 mg ornidazole containing) tablet. The abdominal pain started 2 h after oral intake of ofloxacin-ornidazole FDC tablet obtained without prescription, reaching sufficient severity by 12 h requiring medical consultation in an emergency room. On further questioning, the patient recalled that 3 years ago he had similar abdominal pain that developed after taking ofloxacin-ornidazole FDC (with the different brand name) and had to see a doctor in an emergency. He was diagnosed as acute pancreatitis [Table 1]. The pain of the past episode responded within a few minutes to hours to painkiller injection with a reduction in the food intake on the clinician’s advice. The patient is nonalcoholic; has never smoked or taken any recreational drugs. On evaluation, his vitals were stable. Tenderness was elicited in epigastrium on palpation without any guarding or the rigidity. Biochemical examination showed a raised concentration of lipase 635 units/L and amylase 377 units/L in the serum. CT examination of the abdomen was noteworthy for grade C acute pancreatitis (peripancreatic and perirenal fat stranding) with no collection formation [Figure 1]. Ultrasound examination of the abdomen ruled out the possibility of gallstone [Table 1]. The patient had normal triglycerides and calcium levels had no present or history of sepsis, injury, malignancy, or scorpion bite.

Table 1.

Temporality establishment with laboratory and radiological examination