What is a sulfa drug allergy

People with a known sulfa allergy should always check with their doctor before starting a new medication. This is especially true for those who own had a previous severe reaction.

In addition to oral antibiotics, topical sulfonamides should be avoided. These include:

  1. Silver sulfadiazine ointments used to treat burns
  2. Sulfacetamide eye drops, shampoos, or creams
  3. Sulfanilamide vaginal preparations

Similarly, the oral drug Azulfidine (sulfasalazine), used to treat inflammatory bowel disease and rheumatoid arthritis, should be avoided.

Keep in mind that the risk of cross-reactivity to non-antibiotic sulfonamides is low. This means that it's generally safe to take the following drugs:

  1. Oral sulfonylureas-class drugs used to treat diabetes
  2. Diuretics (water pills) such as HCTZ (hydrochlorothiazide) and Lasix (furosemide)
  3. Celebrex (celecoxib), a COX-2 inhibitor used to treat arthritis and pain


Symptoms

The symptoms and severity of a sulfa allergy can vary but generally involve the appearance of a widespread rash. Occasionally a photosensitive rash may develop, meaning that a rash will happen in areas exposed to sunlight or other UV light while on the medication.

Other serious manifestations of a sulfa allergy include:


Overview

In the majority of cases, a person with a sulfa allergy will own experienced an allergic reaction to one or more of the following antibiotic drugs:

  1. Bactrim (sulfamethoxazole and trimethoprim)
  2. Septra (sulfamethoxazole and trimethoprim)
  3. Pediazole (erythromycin and sulfafurazole)

These reactions are not every that unusual and affect around 3 percent of every people. This is a rate similar to what is seen with other types of antibiotics, including penicillin.

Certain people appear to be at higher risk of sulfa allergy than others.

These include those who, for various reasons, own a suppressed immune system (such as organ transplant recipients and people with HIV/AIDS).


Sulfite and Sulfate Allergies

People will often error a sulfa allergy for a sulfite allergy. Sulfites are preservatives found in foods and medications. These include:

  1. Sodium metabisulfite
  2. Sodium bisulfite
  3. Sodium sulfite
  4. Potassium bisulfite
  5. Potassium metabisulfite

Sulfates are drugs containing sulfuric acid. As with sulfites, sulfates may cause allergy, but the drugs are in no way related to sulfonamides or sulfa-allergy risk.

These include medications such as:

  1. Iron sulfate used to treat iron-deficiency anemia
  2. Albuterol sulfate used to treat bronchial spasms
  3. Chondroitin sulfate used to treat osteoarthritis
  4. Codeine sulfate, an opioid drug used for pain relief

A Expression From Verywell

The nuances of a sulfa allergy can be tricky to tease out, even for some healthcare providers. That's why it's significant to tell your doctor about any prior reaction you may own had to a sulfa medication (or any other drug for that matter).

Sharing that information will make it easier for your doctor to prescribe a substitute that's less likely to cause an allergy.

It's significant to take every drug-related rash seriously, no matter how mild it may be. In some cases, continuing a sulfa-drug while having mild symptoms may cause those mild symptoms to become severe and life-threatening.

While sulfites can cause an ​allergy, there is no direct relationship between a sulfa and sulfite allergy—so someone with a sulfa allergy doesn't own to avoid sulfites (or vice versa).

The following tables list the safety and effectiveness reviews that were started by Health Canada during the identified period.

The appearance of a health product in these tables means that Health Canada has identified a potential safety issue, throughsurveillance, but it does not mean that Health Canada has identified a causal relationship between the health product and the listed risk.

Once a safety and effectiveness review is completed, asummary safety reviewis published to inform Canadians of what was found and what action was taken by Health Canada, if any.

No safety and effectiveness reviews started between 2019-07-01 and 2019-07-31

No safety and effectiveness reviews started between 2019-06-01 and 2019-06-30

No safety and effectiveness reviews started between 2019-05-01 and 2019-05-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Imodium Loperamide hydrochloride Cardiac (heart related) events Foreign agency — The U.S.

Food and Drug istration (US FDA) Safety Communications

Apo-Propylthiouracil, Propyl-Thyracil Propylthiouracil Congenital anomalies (birth defects), neonatal (newborn baby) disorders Foreign agency- European Medicines Agency (EMA)
Janus kinase (JAK) inhibitors: (Xeljanz, Xeljanz XR, Jakavi) Tofacitinib, ruxolitinib Venous Thromboembolic (blood clotting that starts in the vein) events (deep venous thrombosis [DVT] and pulmonary embolism [PE] (blood clots in the lungs)) Drug manufacturer (information from an ongoing study)
Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Imfinzi Durvalumab Hemolytic Anemia (increased red cell destruction and a decreased red cell life span) Drug manufacturer (response to Marketed Health Products Directorate letter)
Ketalar Ketamine Hepatic (liver) disorder Foreign agency — Newsletter from Agence Nationales de Sécurité du Médicament et des Produits de Santé (France)
Breast implants Silicone and saline- filled breast implants Connective tissue, rheumatic, and autoimmune disease (when the immune system attacks its own tissues) Publication
Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger

Daklinza
Galexos
Harvoni
Holkira Pak
Sovaldi
Technivie
Zepatier
Epclusa
Sunvepra
Maviret

Daclatasvir
glecaprevir
ombitasvir
paritaprevir
ritonavir
sofosbuvir
elbasvir
grazoprevir
simeprevir
ledipasvir
dasabuvir
velpatasvir
asunaprevir

Dysglycaemia (abnormality in blood sugar stability – can include low blood sugar or high blood sugar.

European Medicines Agency Assessment

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger

Tapazole
mar-methimazole

Thiamazole

Pancreatitis (inflammation of the pancreas)

European Medicines Agency Assessment

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Daklinza
Galexos
Harvoni
Holkira Pak
Sovaldi
Technivie
Zepatier
Epclusa
Sunvepra
Daclatasvir
ombitasvir
paritaprevir
ritonavir
sofosbuvir
elbasvir
grazoprevir
simeprevir
ledipasvir
dasabuvir
velpatasvir
asunaprevir
Hepatocellular carcinoma (liver cancer) Follow up to previous review completed in 2016

Safety and effectiveness reviews started between 2018-11-01 and 2018-11-30

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) Citalopram,
escitalopram,
fluoxetine
fluvoxamine,
paroxetine,
sertraline, venlafaxine, desvenlafaxine, duloxetine,
bupropion,
mirtazapine
Ongoing sexual dysfunction after stopping the use of the drug Pharmacovigilance Risk Assessment Committee – European Medicines Agency
Breast Implants (Allergan, Inc.; Mentor Medical Systems, B.V; MENTOR; IDEAL) Natrelle saline-filled breast implants (smooth and textured),
natrelle 410 truform silicone-filled breast implants,
natrelle silicone-filled breast implants — biocell round,
natrelle silicone-filled breast implants — smooth round,
natrelle 150 Breast Implants,
natrelle inspira truform 1 (responsive) breast implants — smooth and biocell textured shell,
natrelle inspira truform 2 (soft touch) breast implants — smooth and biocell textured shell,
mentor memorygel cpg gel breast implants — cohesive iii
mentor memory gel silicone gel-filled breast implants – smooth and textured,
memorygel siltex becker expander/ breast implants saline-filled mammary prosthesis – smooth,
smooth spectrum saline filled mammary prosthesis,
siltex spectrum saline-filled mammary prosthesis,
saline-filled mammary prosthesis –textured
mentor memory gel,
silicone gel-filled breast implants – smooth and textured,
ideal implant saline-filled breast implant
Breast implants linked to anaplastic large cell lymphoma — BIA-ALCL (rare type of blood cancer) Many articles and foreign agency notices

Safety and effectiveness reviews started between 2018-10-01 and 2018-10-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Systemic fluroquinolone antibiotics Ciprofloxacin,
levofloxacin,
moxifloxacin,
norfloxacin
Aortic aneurysm (balloon-like bulge in an artery) and dissection (separation or tear in the layers of the wall of the aorta) Pharmacovigilance Risk Assessment Committee – European Medicines Agency
Jardiance,
Qtern,
Synjardy,
Glyxambi,
Xigduo,
Forxiga,
Invokana,
Invokamet,
Invokamet XR,
Steglatro,
Steglujan,
Segluromet
Empagliflozin,
dapagliflozin,
canagliflozin,
ertugliflozin
Fournier’s gangrene — necrotizing fasciitis (progressive inflammatory infection) of the perineum (area between the anus and the scrotum or vulva) Foreign Agency (The U.S Food and Drug istration)
Hormonal contraceptives Levonorgestrel,
etonogestrel,
desogestrel,
norgestrel,
norgestimate,
norethindrone acetate,
norethindrone,
ethynodiol diacetate,
medroxyprogesterone acetate,
norelgestromin,
estradiol valerate,
drospirenone,
ethinyl estradiol
cyproterone acetate
dienogest/estradiol
Suicidality (suicidal thoughts and behaviours) European Medicines Agency
U by kotex sleek tampons (Medical device) N/A Fraying (wearing away) leading to increased risks of toxic shock syndrome and related symptoms Case Report

Safety reviews started between 2018-09-01 and 2018-09-30

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
ACT-propofol
Diprivan
PMS-propofol
Propofol
Propofol injection
Propofol Priapism (persistent and painful erection of the penis) Case reports

Safety reviews started between 2018-08-01 and 2018-08-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Laboratory tests (generic) Laboratory tests (generic) Biotin (vitamin B7) interference with lab tests and potential inappropriate patient management or misdiagnosis Foreign Agency (The U.S Food and Drug istration)
Opdivo,
Yervoy
Nivolumab
Ipilimumamb
Histiocytosis haematophagic (an excessive number of activated macrophages eating blood cells) MBBNHPB Scientific Working Group/ European Medicines Agency

Safety reviews started between 2018-07-01 and 2018-07-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Xarelto Rivaroxaban Liver injury Follow up to previous review completed in 2015

Safety reviews started between 2018-06-01 and 2018-06-30

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Avalon fetal monitor (FM20, FM30, FM40, FM50)
(medical device)
N/A Inaccurate ultrasound-derived fetal heart rate readings (device error in the results of unborn baby’s heart beat) Incident report
Hydrochlorothiazide Hydrochlorothiazide Non melanoma (all types of skin cancer that are not melanoma) Publication

Safety reviews started between 2018-05-01 and 2018-05-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Ferriprox Deferiprone Neurological disorders (conditions related to the brain or central nervous system) in children at recommended dosage Publication
Gilenya Fingolimod
hydrochloride
Rebound effect (emergence or re-emergence of symptoms) with product withdrawal. Foreign Agency — Signal Identification from Foreign Agencies

Safety reviews started between 2018-04-01 and 2018-04-30

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
APO-sulfatrim DS TAB,
APO-sulfatrim pediatric,
APO-sulfatriM TAB,
Protrin DF TAB,
Septra injection,
TEVA-trimel,
TEVA-trimel DS
Sulfamethoxazole
trimethoprim
Drug reaction with eosinophilia and systemic symptoms (DRESS) Drug manufacturer (Voluntary Post Market Vigilance)
Opsumit Macitentan Liver injury Drug manufacturer (Periodic Safety Update Report (PSUR))

Safety reviews started between 2018-03-01 and 2018-03-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue Trigger
Contact lenses

(medical devices)

N/A Limbal stem cell deficiency (loss of stem cells (cells that can develop into diverse types of cell) in the limbus (border of the cornea and the sclera)) Publication
Liquid-filled intragastric balloon

(medical device)

Orbera system,
endball system,
reshape device,
spatz3 system

Death, acute pancreatitis (sudden inflammation of the pancreas), gastric perforation ( hole that develops through the wall of the stomach), esophageal perforation (hole in the esophagus), spontaneous over-inflation (sudden excessive increase in size) Foreign Agency ( The U.S.

Food and Drug istration (US FDA)

Prescription opioids — cough and freezing indication Codeine,
hydrocodone
Opioid use disorder (misuse/overdose) in pediatrics (children) US FDA
Urogynaecological (transvaginal) synthetic meshes

(medical devices)

N/A Various mesh (net-like implant) related complications Many sources including previous Health Canada Safety Reviews

Safety reviews started between 2018-02-01 and 2018-02-28

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Fibristal, Ella Ulipristal Serious liver injury
Toujeo, Lantus Insulin glargine Potential association of breast cancer with long-term use

Safety reviews started between 2018-01-01 and 2018-01-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
APO-prednisone tablet,

NU-prednisone, Prednisone tablet, TEVA-prednisone, Methylprednisolone sodium succinate for injection, PMS-prednisolone

Prednisolone and prednisone Scleroderma renal crisis (fatal complication of scleroderma (abnormal growth of connective tissue) characterized by severe hypertension and renal (kidney) failure)fatal complication of scleroderma fatal complication of scleroderma fatal complication of scleroderma
Imbruvica Ibrutinib Ventricular arrhythmias (abnormal heart rhythm that comes from an area of the lower chamber (ventricle) of the heart) and sudden death
Metadol-D, Methadose Methadone hydrochloride Pharmacogenetic predisposition (how people reply differently to medicines due to their genetic inheritance) to methadone in children exposed to methadone through breast feeding

Safety reviews started between 2017-12-01 and 2017-12-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Antibiotics:

(Ceftriaxone for injection,
Ceftriaxone for injection USP, Ceftriaxone sodium for injection, Ceftriaxone sodium for injection BP, Ceftriaxone sodium for injection, BP Amoxi-Clav, Amoxicillin, Amoxicillin capsules, Amoxicillin granules for oral suspension, APO-Amoxicillin capsules 250mg,
APO-Amoxicillin capsules 500mg, APO-Amoxi Clav 250/125, APO-Amoxi Clav 500/125, APO-Amoxi Clav 875/125, APO-Amoxicillin powder for suspension 125mg/5ml, APO-Amoxicillin powder for suspension 250mg/5ml, APO-Amoxicillin sugar free, AURO-Amoxicillin,
Clavulin 125 F oral suspension,
Clavulin 200, Clavulin 250 F oral suspension, Clavulin 400,
Clavulin 500 F tablet, Clavulin 875, HP-PAC JAMP-Amoxicillin,
MYLAN-Amoxicillin, PMS-Amoxicillin, PRO -Amoxicillin -500 capsules 500mg, PRO-Amoxicillin — 250 oral suspension, 250mg/5ml,
RATIO-Aclavulanate, RATIO-Aclavulanate 250 F

Ceftriaxone sodium,
amoxicillin, amoxicillin trihydrate
Drug reaction with eosinophilia and systemic symptoms (DRESS), Severe cutaneous (skin) adverse reactions (SCAR)
Jakavi Ruxolitinib phosphate Potential drug interaction (with Crestor) due to suppression of p-glycoprotein

Safety reviews started between 2017-11-01 and 2017-11-30

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Remicade, Inflectra,
Remsima
Infliximab Linear IgA bullous dermatosis (rare disease due to autoimmune reaction)
VEGF Receptor Inhibitors:

(Caprelsa, Iclusig,
Inlyta, Lenvima,
Nexavar, Stivarga
Sutent, Votrient)

Axitinib, lenvatinib,
pazopanib, ponatinib,
regorafenib, sorafenib,
sunitinib, vandetanib
Aortic dissection (serious condition in which the inner layer of the aorta, the large blood vessel branching off the heart, tears)

Safety reviews started between 2017-10-01 and 2017-10-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Jardiance, Qtern,
Synjardy, Glyxambi,
Xigduo, Forxiga, Invokana,
Invokamet
Empagliflozin, linagliptin,
dapagliflozin, saxagliptin,
metformin hcl, canagliflozin
Chronic pancreatitis (progressive inflammatory disease of the pancreas), acute pancreatitis (sudden inflammation of the pancreas)
Metadol-D,
Methadose
Methadone hydrochloride Pharmacogenetic predisposition (how people reply differently to medicines due to their genetic inheritance) to methadone in children exposed to methadone through breastfeeding

Safety reviews started between 2017-09-01 and 2017-09-30

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Metal-containing orthopedic hip implants (medical device) N/A Systemic (throughout the body) health consequences

Safety reviews started between 2017-08-01 and 2017-08-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Gleevec Imatinib Tendon disorders (disorders affecting a flexible but non-elastic piece of tissue in the body attaching a muscle to a bone)
PDP-Isoniazid Isoniazid Pancreatitis (inflammation of the pancreas)
Sunscreen Sunscreen products containing avobenzone, homosalate, octinoxate, octisalate, octocrylene and oxybenzone Hypersensitivity (abnormal reaction) and skin burn-type reactions

Safety reviews started between 2017-07-01 and 2017-07-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Halaven Eribulin mesylate Severe cutaneous (skin) adverse reactions (SCAR)
SGLT2 inhibitors

(Jardiance, Qtern,
Synjardy, Glyxambi,
Xigduo, Forxiga,
Invokana, Invokamet)

Empagliflozin, linagliptin,
dapagliflozin, saxagliptin,
metformin hcl,
canagliflozin
Posterior reversible encephalopathy syndrome (PRES)
(rare brain condition) in association with diabetic ketoacidosis (high levels of acids in the blood)
Therapy ablation catheters
(medical devices)
N/A Atrioesophageal fistula (AEF) (abnormal connection between the heart and digestive tract)

Safety reviews started between 2017-06-01 and 2017-06-30

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Omnipod insulin management system (medical device) N/A Hyperglycemia (a condition in which too much glucose is in the blood)
Sevoflurane AF, generics Sevoflurane Bradycardia (a slower than normal heart rate) in children with Below Syndrome (a condition in which additional genetic material causes delays in the way a kid develops, both physically and mentally)

Safety reviews started between 2017-05-01 and 2017-05-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Abilify, Saphris Clozaril, Latuda Zyprexa, Invega Invesga sustenna, Invega trinza, Seroquel, Seroquel xr Risperdal, Risperdal Consta, Zeldox Aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, paliperidone palmitate, quetiapine, quetiapine fumarate, risperidone, ziprasidone Drug reaction with eosinophilia and systemic symptoms (DRESS) (skin rash caused by a drug with increased white blood cell counts and symptoms in every parts of the body)
Enterra Therapy System (medical device) N/A Lack of effectiveness
Pradaxa Dabigatran Liver injury

Safety reviews started between 2017-04-01 and 2017-04-30

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Avonex Interferon beta-1a Sarcoidosis (disease involving the growth of tiny groups of inflammatory cells in diverse parts of the body — generally the lungs, lymph nodes, eyes and skin)
Trajenta, Januvia, Janumet, Janumet XR, Nesina, Kazano, Jentadueto, Onglyza, Komboglyze, Oseni, Qtern, Glyxambi Linagliptin, sitagliptin alogliptin, saxagliptin, linagliptin and metformin, alogliptin and metformin, saxagliptin and metformin, sitagliptin and metformin alogliptin and pioglitazone, saxagliptin and dapagliflozin, linagliptin and empagliflozin Bullous pemphigoid (rare skin condition that causes large pockets of body fluid)

Safety reviews started between 2017-03-01 and 2017-03-31

Brand Name and/ or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Gilenya Fingolimod Thrombocytopenia (a condition in which the blood platelet count is low)
Viscoelastic devices:
Duovisc viscoelastic solution,
provisc viscoelastic solution,
viscoat ophthalmic viscoelastic device,
cellugel viscosurgical device,
discovisc ophthalmic viscosurgical device (medical devices)
N/A Toxic Anterior Segment Syndrome (TASS) (an acute inflammatory reaction in which a noninfectious substance enters the eye anterior segment and induces toxic damage to the surrounding tissues)
Zydelig Idelalisib Progressive multifocal leukoencephalopathy (a serious brain infection)

Safety reviews started between 2017-02-01 and 2017-02-28

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Effient Prasugrel hydrochloride Severe cutaneous (skin) adverse reactions (SCAR)
Fluconazole Fluconazole Spontaneous abortion/ miscarriage (loss of the fetus (unborn baby)) and congenital malformation (increased risk of birth defects)
Jakavi Ruxolitinib Liver injury including liver failure
TactiCath Quartz contact force ablation catheter (medical device) N/A Cardiac tamponade (medical condition in which blood or fluids fill the space between the sac that envelops the heart and the heart muscle)

Safety reviews started between 2017-01-01 and 2017-01-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Atypical antipsychotics Aripiprazole, paliperidone risperidone, asenapine quetiapine, ziprasidone olanzapine Complex sleep-related behaviour
Product Pump Inhibitors (PPI) Omeprazole, pantoprazole lansoprazole, rabeprazole esomeprazole, dexlansoprazole Drug-induced subacute cutaneous lupus erythematosus (an autoimmune disease whereby the immune system may attack some parts of the body and cause skin lesions.

This condition can be caused by medication)

Specific benzodiazepines and barbiturates used in the setting of general anaesthesia and/or sedation (a relaxed, calm, or sleepy condition that results from taking a drug) Lorazepam, midazolam phenobarbital, thiopental Neurodevelopmental toxicity (toxicity affecting the development of the brain or central nervous system)

Safety reviews started between 2016-12-01 and 2016-12-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Breast implant (medical device) N/A Breast implant associated -anaplastic large cell lymphoma (ALCL) (a rare cancer of the immune system)
General anesthetics (part 1) Desflurane, Isoflurane, ketamine, Propofol, sevoflurane Neurodevelopmental toxicity (toxicity affecting the development of the brain or central nervous system)
Infusion pump with/without master drug library (medical device) N/A Various device failures (break down)
Lariam (discontinued), Mefloquine Mefloquine Long term neurological (related to the brain or central nervous system) and psychiatric adverse events
Mirena, Jaydess Levonorgestrel Suppressed lactation (blocked secretion of milk by the mammary glands)

Safety reviews started between 2016-11-01 and 2016-11-30

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Aubagio Teriflunomide Colitis (inflammation of the large intestine (colon))
Quill knotless tissue-closure devices (medical device) N/A Intestinal obstruction/volvulus (blockage that keeps food or liquid from passing through the intestine)

Safety reviews started between 2016-10-01 and 2016-10-31

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Aubagio Teriflunomide Acute renal (sudden kidney) failure

Safety reviews started between 2016-09-01 and 2016-09-30

Brand Name and / or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Aerius Deloratadine QT prolongation and torsade de pointes (heart rhythm problem)
Brilinta Ticagrelor Severe (skin) cutaneous adverse reactions (SCAR)
Green Tea Green tea extract Liver injury
Parenteral nutrition solutions
(Primene, Prosol, Clinimix, Olimel, Travasol, Smofkabiven, Aminosyn)
Amino acid Increased mortality in pre-term infants (premature babies who are born before 37 completed weeks of gestation) when solution is not shielded (protected) from light
Tecfidera Dimethyl fumarate Renal (kidney) injury, including acute renal failure

Safety reviews started between 2016-08-01 and 2016-08-31

Brand Name and/or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
DPP-4 inhibitors Alogliptin, linaglipton, sitaglipton, saxaglipton Heart failure
Heater-cooler system N/A Contamination/infections
Intraocular lens N/A Development of glistening (sparkling or shining reflection) in intraocular lens
Iodine contrast agents Diatrizoate, iodipamide, iopamidol, ioxitalamate, ioversol, iothalamate, iodixanol, iohexol, iopromide Hypothyroidism (abnormally low activity of the thyroid gland)
Proscar, Propecia Finasteride Muscle-related side effects
Voluven, Volulyte Hydroxyethyl starch Acute kidney injury in non-critically ill trauma, and elective surgery patients (sudden kidney injury in patients who are injured but not extremely ill or own had surgery that is not urgent)

Safety reviews started between 2016-07-01 and 2016-07-31

Brand Name and/or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Direct-acting antivirals indicated for the treatment of hepatitis C (Daklinza, Epclusa, Galexos, Harvoni, Holkira Pak, Sovaldi, Technivie, Zepatier) Asunaprevir, daclatasvir, dasabuvir, elbasvir, grazoprevir, ledipasvir, ombitasvir, paritaprevir, ritonavir, simeprevir, sofosbuvir, velpatasvir Early recurrence of hepatocellular carcinoma (liver cancer)
Direct-acting antivirals indicated for the treatment of hepatitis C (Daklinza, Epclusa, Galexos, Harvoni, Holkira Pak, Sovaldi, Technivie, Zepatier) Asunaprevir, daclatasvir, dasabuvir, elbasvir, grazoprevir, ledipasvir, ombitasvir, paritaprevir, ritonavir, simeprevir, sofosbuvir, velpatasvir Hepatitis B reactivation

Safety reviews started between 2016-06-01 and 2016-06-30

Brand Name and/or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Aclasta, Zometa, Fosamax, Fosavance, Bonefos, Clasteon, Didrocal, Etidrocal Pamidronate, Actonel, Actonel DR Zoledronic acid, alendronate, clodronate etidronate, pamidronate risedronate Non-mandibular osteonecrosis (death of tissue in bones other than the jaw)
Hospital beds Hospital beds Entrapment (patient is caught in the spaces between the bed rail, mattress or hospital bed frame)

Safety reviews started between 2016-05-01 and 2016-05-31

Brand Name and/or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Stent system Esophageal stent systems Erosion of vascular structure (wearing away of blood vessels)

Safety reviews started between 2016-04-01 and 2016-04-30

Brand Name and/or Product Class/ Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Dipeptidylpeptidase-4 (DPP-4) inhibitors

(Januvia, Janumet, Onglyza, Komboglyze, Trajenta, Jentadueto, Nesina, Kazano, Oseni)

Sitagliptin, saxagliptin, linagliptin, alogliptin, (metformin combination) Serious arthralgia (joint pain)
Gadolinium containing products

(Magnevist, Gadovist, Omniscan, Multihance, Optimark, Prohance, Primovist)

Gadoversetamide, gadobutrol, gadopentetate, gadobenate, dadodiamide, gadoteridol, gadoxetate Build-up of the Gadolinium containing products in the brain
Tysabri Natalizumab Hematological disorders (disorders mainly affecting the blood) in neonates (newborns)
Xalkori Crizotinib Gastrointestinal perforation (hole that develops through the wall of the stomach, little intestine, large intestine, gallbladder or rectum
Zydelig Idelalisib Serious infections/death

Safety reviews started between 2016-03-01 and 2016-03-31

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Antidepressants Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline Autism spectrum disorders (a group of disorders that shows a lack of social skills, difficulty in communicating, repeating behaviours, and a slow mental development) in children
Avastin Bevacizumab Non-mandibular osteonecrosis (death of tissue in bones other than the jaw) in adult population
Counterirritants containing menthol, methyl salicylate or capsaicin Menthol, methyl salicylate and capsaicin Serious skin burns

Safety reviews started between 2016-02-01 and 2016-02-29

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Accutane Isotretinoin Erectile dysfunction (the inability to get and hold an erection firm enough for sex)
Aclasta, Aredia, Bonefos, Clasteon Zoledronic acid, pamidronate, clodronate (injectable bisphosphonate) Osteonecrosis of the jaw (a severe bone disease that affects the jaw)
Amiodarone hydrochloride for injection Amiodarone hydrochloride Fetal (unborn baby) and neonatal (newborn) side effects including cardiac and neurodevelopmental events (development of the brain or central nervous system)
Cervarix Human papillomavirus Types 16 and 18 (Recombinant, AS04 adjuvanted) Guillain-Barré syndrome (a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system)
Keppra Levetiracetam Impaired renal (kidney) function
Systemic fluoroquinolone antibiotics Ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin Persistent disabilities: skeletal muscular, neuro-psychiatric (mental disorders related to diseases of the nervous system), tendonitis (inflammation of a tendon), peripheral neuropathy (damage to or disease affecting peripheral nerves), vision disturbances and phototoxicity (skin irritations caused by chemicals reacting to light)

Safety reviews started between 2016-01-01 and 2016-01-31

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Codeine (prescription codeine-containing products for pain) Codeine Fatal (causing death) and life-threatening respiratory side effects (very slow breathing requiring emergency care) in children and adolescents (up to 18 years of age)
Loratadine Loratadine QT prolongation and torsade de pointes (heart rhythm problem)
Phenylephrine Phenylephrine Phenylephrine drug interaction with acetaminophen

Safety reviews started between 2015-12-01 and 2015-12-31

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Clozaril, Clozapine Clozapine Hematological monitoring (monitoring of disease of the blood and bone marrow)
Codeine (non-prescription codeine-containing products (for cough and freezing and pain/antipyretic)) Codeine Risk of respiratory depression in children and adolescents (up to 18 years of age)
Januvia, Janumet, Janumet XR, Onglyza, Komboglyze & Trajenta, Jentadueto, Nesina, Kazano Sitagliptin, linagliptin, alogliptin, saxagliptin Gastrointestinal obstruction (blockage that keeps food or liquid from passing through the intestine)
Neurontin, Gabapentin Gabapentin Life-threatening respiratory depression (very slow breathing requiring emergency care), without concomitant opioid use
Zelboraf Vemurafenib Bone marrow toxicity/suppression (white blood cells suppression)
Zofran Ondansetron hydrochloride dehydrate Fetal (unborn baby) harm

No safety reviews were started between 2015-11-01 and 2015-11-30

Safety reviews started between 2015-10-01 and 2015-10-31

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Forxiga, Invokana, Jardiance (SGLT2 class inhibitors) Dapagliiflozin, canagliflozin, empagliflozin Increased risk of bone fractures, due to loss of bone mineral density
Avonex, Betaseron, Extavia, Plegridy, Rebif
(Beta-interferons)
Interferon beta Risk of pulmonary arterial hypertension (type of high blood pressure that affects the arteries in the lungs and the correct side of the heart).

Safety reviews started between 2015-07-01 and 2015-09-30

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Atypical Antipsychotic: Abilify, Clozaril, Invega, Latuda, Risperdal, Seroquel, Zeldox, Zyprexa Aripiprazole, clozapine, paliperidone, lurasidone, risperidone, quetiapine, ziprasidone, olanzapine Urinary retention (temporary difficulty urinating and incomplete bladder emptying)
Bexsero Neisseria meningitidis group B Safety of vaccination with Bexsero in older patients
Digoxin, Apo-Digoxin, Lanoxin, PMD-digoxin, Toloxin Digoxin Increased mortality (death)
Dimetane Expectorant DC, Tussionex, PMS-hydrocodone, Novahistine, Dalmacol, Hycodan, Novahistex DH, Ratio-calmydone, Tramacet, Zytram, Tridural, Ralivia, Ultram, Durela, and generic formulations of tramadol. Hydrocodone and tramadol containing products Life-threatening respiratory depression (very slow breathing requiring emergency care) in children
Estrogen-only hormone replacement therapy (C.E.S., Climara, Divigel, Estrace, Estradot, Estragyn, Estring, Estrogel, Oesclim, Premarin, Vagifem)

Estrogen and progestogen combination hormone replacement therapy (Activelle, Angeliq, Climara Pro, Estalis, Estrogel Propak, FemHRT, Prefesta, Premplus)

Progestogen-only for use with estrogen replacement therapy (Prometrium, Provera)

Estrogen and selective estrogen receptor modulator combination (Duavive)

Selective estrogen receptor modulator (Evista)

17β-Estradiol, conjugated estrogens, estrone, ethinyl estradiol

Drospirenone, progesterone, levonogestrel, medroxyprogesterone, norethindrone, norgestimate

Bazedoxifene, raloxifene,

Ovarian cancer in menopausal women (a type of cancer detected in the ovaries)
Exelon Rivastigmine hydrogen tartrate Increased mortality (death)
Gilenya Fingolimod Progressive multifocal leukoencephalopathy (a serious brain infection)
Gilenya Fingolimod Malignancies (tumors which are cancerous and can cause serious illness or death), neoplasms (new and abnormal growth of tissues)
Havrix Hepatitis A inactivated Immune thrombocytopenic purpura (ITP) (a disorder that can lead to simple or excessive bruising and bleeding)
Intuniv XR Guanfacine hydrochloride Raynaud’s phenomenon (disorder that causes some areas of the body to feel numb and freezing as a result of a limited blood circulation)
Keppra Levetiracetam Drug-drug interaction with methotextrate
Proscar and Propecia Finasteride Convulsions (seizures)
Soliris Eculizumab Use of Soliris in patients that are receiving meningococcal B vaccine at the same time
Yondelis Trabectedin Capillary leak syndrome (disorder that can lead to a leak of fluid from the blood vessels into the body’s tissues)

Safety reviews started between 2015-04-01 and 2015-06-30

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Alpha-lipoic acid Alpha-lipoic acid Insulin autoimmune syndrome (IAS) or Hirata’s disease (rare disorder characterized by hypoglycemia caused by insulin autoantibodies)
Atypical antipsychotic: Abilify, Clozaril, Invega, Latuda, Risperdal, Seroquel, Zeldox, Zyprexa Aripiprazole, clozapine, paliperidone, lurasidone, risperidone, quetiapine, ziprasidone, olanzapine Sleep apnea (serious sleep disorder in which breathing repeatedly stops and restarts)
Diclectin Doxylamine — pyridoxine HCL Adverse/neonatal outcomes
Forxiga, Invokana Dapagliflozin, canagliflozin Ketoacidosis (high blood levels of ketones (acids))
Sudafed 120 mg Pseudoephedrine Ischemic colitis (blood flow to part of the large intestine (colon) is decreased due to narrowed or blocked blood vessels (arteries))
Tysabri Natalizumab Hemolytic anaemia (increased red cell destruction and a decreased red cell life span)
Velcade Bortezomib Necrotizing fasciitis (rare bacterial infection also called flesh-eating disease)

Safety reviews started between 2015-01-01 and 2015-03-31

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Avastin bevacizumab Vocal cord necrosis (death of cells or tissue of the vocal cord)
Avonex interferon beta-1a Risk of nephrotic syndrome (a collection of symptoms that indicate kidney damage)
Chlorhexidine solutions chlorhexidine Anaphylactic reactions (severe allergic reactions)
Chlorhexidine solutions chlorhexidine Skin injuries, including burns, in premature infants
Cimzia certolizumab Autoimmune hepatitis (inflammation of the liver that occurs when the body’s immune system attacks the liver)
Codeine-containing products Codeine Death and life threatening adverse events in children
Eprex epoetin alfa Evaluation of a new method for calculating the number of patients exposed to the drug
Eylea aflibercept Higher systemic exposure after intravitreal injection (higher levels of the medicine in the body after injection into the eye) compared to the drug ranibizumab
Gardasil recombinant human papillomavirus type 6L1, 11L1, 16L1, 18L1 protein Associated adverse events with a focus on autoimmune diseases (when the immune system attacks the body) and cardiovascular diseases (involving the heart or blood vessels)
Humira adalimumab Autoimmune hepatitis (inflammation of the liver that occurs when the body’s immune system attacks the liver)
Invokana canagliflozin Renal impairment (inability of the kidneys to work properly)
Lidocaine, topical oral anesthetic viscous lidocaine Serious adverse reactions in infants and young children, including seizure, severe brain injury, heart problems, and death
Prolia and Xgeva denosumab Deafness
Simponi golimumab Autoimmune hepatitis (inflammation of the liver that occurs when the body’s immune system attacks the liver)
Tazocin piperacillin-tazobactam (combination) Drug rash with eosinophilia and systemic symptoms (DRESS) (skin rash caused by a drug with increased white blood cell counts and symptoms in every parts of the body)
Uloric febuxostat Heart failure
WinRho SDF RhoD immune globulin (human) Reactions linked the manufacturing of the product

Safety reviews started between 2014-10-01 and 2014-12-31

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Actos pioglitazone HCL Bladder cancer
Antidepressants desipramine; imipramine; clomipramine; doxepin; trimipramine; amitriptyline; nortriptyline; maprotiline; mirtazapine; phenelzine; tranylcypromine; moclobemide; fluoxetine; citalopram; paroxetine; sertraline; fluvoxamine; escitalopram; venlafaxine; desvenlafaxine; duloxetine; trazodone; bupropion Angle-closure glaucoma (increased eye pressure)
Clear Care cleaning and disinfecting solution for contact lenses 3% hydrogen peroxide Eye injuries
Enbrel etanercept Increased risk of congenital malformation (increased risk of birth defects)
Galexos simeprevir Remarkable increase in blood bilirubin level
Helixate FS and Kogenate FS antihemophilic factor (recombinant) Higher risk of inhibitor development in previously untreated patients compared to another widely used product (higher risk of developing antibodies that can reduce how well the treatment works in patients receiving the product for the first time)
Melatonin melatonin Use of melatonin in children
Octagam 5% and 10% immunoglobulin G (human) Lack of efficacy, and safety issues relating to the modifications of the manufacturing process (hypersensitivity, thrombosis)
Perjeta pertuzumab Stevens-Johnson syndrome (life-threatening skin condition)
Uloric febuxostat Drug rash with eosinophilia and systemic symptoms (DRESS) (skin rash caused by a drug with increased white blood cell counts and symptoms in every parts of the body)
Uloric febuxostat Hematological effects (Effects related to the blood and blood forming organs)
Velcade Bortezomib Necrotizing fasciitis (flesh-eating disease)
Xarelto rivaroxaban Liver injury
Yervoy ipilimumab Drug rash with eosinophilia and systemic symptoms (DRESS) (skin rash caused by a drug with increased white blood cell counts and symptoms in every parts of the body)

Safety reviews started between 2014-07-01 and 2014-09-30

Brand Name or Product Class / Medical Device(s) Medicinal Ingredient(s) Potential Safety Issue
Atarax hydroxyzine QT prolongation and torsade de pointes (heart rhythm problem)
Celebrex celecoxib Arterial thromboembolism (blocking of an artery)
Enbrel etanercept Schizophrenia-like disorders
Gleevec imatinib mesylate Chronic renal impairment (chronic kidney disease)
Revolade eltrombopag Severe skin reactions
Tumour necrosis factor alfa (TNF α) inhibitors certolizumab pegol, etanercept, adalimumab, infliximab, golimumab Glioblastoma (type of brain tumour)
Topical benzoyl peroxide-containing products benzoyl peroxide Hypersensitivity/ anaphylactic reactions (severe allergic reactions)



NOVI, Mich.

— ALLERGIC reactions to antibiotics can be severe, including symptoms ranging from hives and wheezing to anaphylactic shock. People with such allergic reactions are correct to steer clear. The problem is that numerous, and probably most, people who tell they’re allergic to antibiotics actually aren’t. For penicillin, the most commonly reported allergy, numerous studies own estimated that up to 90 percent of claims of allergies are not legitimate.

Why would someone tell they were allergic to an antibiotic if they weren’t?

Some people own been incorrectly told by their parents that they had an allergic reaction as a kid. Often, they had a side effect love nausea, diarrhea or headache.

What is a sulfa drug allergy

But a true allergic reaction is extremely different: Your body treats the medication as if it is an invader and releases chemicals to attack it. Contrary to favorite belief, these reactions do not happen the first time you are exposed to a medication, because your body must be primed to recognize it. And some people simply don’t love the thought of taking a medication and list it as an allergy so they will never be given it.

Whatever the reason, this decision to limit the number of drugs you can get could own fatal consequences, especially now, with the rise of “superbugs” that are resistant to numerous antibiotics.

Five years ago, when I was a resident physician at a hospital, I had a patient with one of these bugs, a rare helpful of pneumonia that she had acquired after chemotherapy weakened her immune system. There were only a few antibiotics that were capable of treating it, and I ordered the one that was most effective, a sulfa drug. Later I received a call from her nurse stating that the patient was allergic to the medication. As the patient had reported no drug allergies to me, I went to her bedside to investigate.

Even with the best drug, her chances of survival were only 50/50, so this was a matter of life or death.

Bactrim is the brand name of the generic antibiotic sulfamethoxazole trimethoprim (sometimes called co-trimoxazole).

The drug is a combination of two antibiotics: It’s one part trimethoprim (a synthetic drug), and five parts sulfamethoxazole (a sulfonamide drug).

Bactrim works against bacteria in the following types of infections:

  1. Urinary tract infections (UTIs) caused byE. coli, Klebsiella, Enterobacter, Morganella morganii, Proteus mirabilis, and Proteus vulgaris
  2. Middle-ear infections (acute otitis media) in children if they’re caused by the bacteria Streptococcus pneumoniae and Haemophilus influenzae
  3. Chronic bronchitis when it worsens (acute exacerbations) and is caused by Streptococcus pneumoniae or Haemophilus influenzae
  4. Some types of diarrhea, including dysentery, caused by Shigella flexneri and S.

    sonnei infections; and traveler’s diarrhea, caused by enterotoxigenic E. coli

  5. Pneumonia caused by Pneumocystis jiroveci: for treatment, and sometimes for prevention when your immune system is compromised by immunosuppressant drugs or HIV/AIDS

Bactrim is also sometimes prescribed for other types of bacterial pneumonia, for acne, and for preventing urinary tract infections.

The Food and Drug istration (FDA) first approved Bactrim in 1973. The drug is made by Mutual Pharmaceutical Co.

Bactrim Warnings

Bactrim shouldn’t be used by people who:

  1. Are hypersensitive to trimethoprim or sulfonamide drugs (or own sulfa allergies)
  2. Have suffered from thrombocytopenia (low blood platelet count) after taking trimethoprim or sulfonamides
  3. Have megaloblastic anemia (low red blood cell count) caused by a folic acid deficiency
  4. Are less than two months old
  5. Have severe liver damage or poor kidney function that cannot be monitored

Though rare, the use of sulfonamides can cause severe and potentially fatal reactions, such as Stevens-Johnson syndrome.

Stop taking Bactrim and call your doctor correct away if you develop a rash after taking Bactrim, and get emergency medical assist if the rash starts to become severe or you feel love you are having an allergic reaction.

Other rare but serious reactions own included toxic epidermal necrolysis (a life-threatening skin condition), acute liver failure, agranulocytosis (severely low levels of white blood cells), aplastic anemia (when the body stops blood cell production), and other blood-related disorders.

As with most other antibiotics, Bactrim may cause prolonged diarrhea resulting from a difficult-to-treat Clostridium difficile (C.

diff) infection.

Before taking Bactrim, also tell your doctor if you have:

  1. Folic acid deficiency
  2. Kidney or liver disease
  3. An inherited blood disease called glucose-6-phosphate dehydrogenase (G-6-PD) deficiency
  4. Severe allergies
  5. Bronchial asthma
  6. A thyroid disorder
  7. HIV/AIDS
  8. Porphyria, an inherited enzyme disease that may cause skin and nervous system problems
  9. Phenylketonuria, an inherited disorder that can cause intellectual disabilities if a strict diet is not maintained

Pregnancy and Bactrim

Bactrim may harm a developing fetus.

The drug has a warning that if you take it when you’re pregnant, it can cause such birth defects as urinary tract defects, cleft lip or palate, or club feet.

Before taking Bactrim, tell your doctor if you are pregnant or may become pregnant.

It should only be used during pregnancy if the benefits clearly outweigh the potential harms to the unborn child.

You should not breastfeed when taking Bactrim.

The drug is excreted in breast milk and has the potential to harm breastfeeding infants, especially if they are ill, stressed, or premature.

Sulfatrim S/S

Generic Name: Sulfonamides and Trimethoprim
This monograph includes information on the following:

1) Sulfadiazine and Trimethoprim*
2) Sulfamethoxazole and Trimethoprim

BAN:
{04}Sulfadiazine—Sulphadiazine
Sulfamethoxazole—Sulphamethoxazole

JAN:
{04}Sulfamethoxazole—Acetylsulfamethoxazole
Sulfamethoxazole—Sulfamethoxazole sodium

VA CLASSIFICATION
Primary: AM650

Commonly used brand name(s): Apo-Sulfatrim2; Apo-Sulfatrim DS2; Bactrim2; Bactrim DS2; Bactrim I.V.2; Bactrim Pediatric2; Cofatrim Forte2; Coptin1; Coptin 11; Cotrim2; Cotrim DS2; Cotrim Pediatric2; Novo-Trimel2; Novo-Trimel D.S.2; Nu-Cotrimox2; Nu-Cotrimox DS2; Roubac2; Septra2; Septra DS2; Septra Grape Suspension2; Septra I.V.2; Septra Suspension2; Sulfatrim2; Sulfatrim Pediatric2; Sulfatrim S/S2; Sulfatrim Suspension2; Sulfatrim-DS2.

Other commonly used names are

• Cotrimazine Sulfadiazine and Trimethoprim

• Cotrimoxazole Sulfamethoxazole and Trimethoprim

• SMZ-TMP Sulfamethoxazole and Trimethoprim
Note:For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Category:

Antibacterial (systemic)—Sulfadiazine and Trimethoprim; *Sulfamethoxazole and Trimethoprim;

Antiprotozoal—Sulfamethoxazole and Trimethoprim;

Indications

Note:Bracketed information in the Indications section refers to uses that are not included in U.S.

product labeling.

General considerations
Sulfonamides, such as sulfadiazine and sulfamethoxazole, used together with trimethoprim, produce synergistic antibacterial activity. {14}{156} Sulfadiazine and sulfamethoxazole own equal antibacterial properties, covering the same spectrum of activity. {14}These sulfonamides, in combination with trimethoprim, are athletic in vitro against numerous gram-positive and gram-negative aerobic organisms. They own minimal activity against anaerobic bacteria. {104} Susceptible gram-positive organisms include numerous Staphylococcus aureus , including some methicillin-resistant strains, S.

saprophyticus , some group A beta-hemolytic streptococci, Streptococcus agalactiae , and most but not every strains of S. pneumoniae . {104} Gram-negative organisms that are susceptible include Escherichia coli, numerous Klebsiella species, Citrobacter diversus and C. fruendii , Enterobacter species, Salmonella species, Shigella species, Haemophilus influenzae , including some ampicillin-resistant strains, H.

ducreyi , Morganella morganii , Proteus vulgaris and P. mirabilis , and some Serratia species. {104} Sulfonamide and trimethoprim combinations also own activity against Acinetobacter species, Pneumocystis carinii, Providencia rettgeri , P. stuarti , Aeromonas , Brucella , and Yersinia species. {104} They are also generally athletic against Neisseria meningitidis , Branhamella (Moraxella) catarrhalis , and some, but not every, N.

gonorrhoeae . {104}Pseudomonas aeruginosa is generally resistant, but P. cepacia and P. maltophilia may be sensitive. {104}

The major difference between sulfadiazine and sulfamethoxazole exists in their respective pharmacokinetics. The primary distinction is that sulfadiazine is metabolized to a much lesser extent than is sulfamethoxazole. {14}{152}{156} This allows for a higher urinary concentration of unchanged sulfadiazine {152}{156}{164}, as well as an increased risk of crystalluria when it is istered in high doses {152}; the antibacterial urinary concentration of sulfadiazine is maintained over a 24-hour interval, allowing for once-a-day dosing in adults.

{150}{164} Also, sulfadiazine achieves higher concentrations in the bile and cerebrospinal fluid. {14}{151}

Accepted

Bronchitis (treatment)—Oral sulfamethoxazole and trimethoprim combination is indicated in adults in the treatment of acute exacerbations of chronic bronchitis caused by susceptible organisms. {03}{05}{18}{22}{38}{168}{170}

Enterocolitis, Shigella species (treatment) —Oral and parenteral sulfamethoxazole and trimethoprim combinations are indicated in the treatment of enterocolitis caused by susceptible strains of Shigella flexneri and S.

sonnei.{01}{03}{05}{21}{38}{168}{169}{170}{171}

Otitis media, acute (treatment)—Oral sulfamethoxazole and trimethoprim combination is indicated in the treatment of acute otitis media caused by susceptible organisms in children. {03}{05}{21}{38}{168}{170}

Pneumonia, Pneumocystis carinii (prophylaxis)1—Oral sulfamethoxazole and trimethoprim combination is indicated in the prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients who are immunocompromised and considered to be at increased risk of developing PCP, including patients with acquired immunodeficiency syndrome (AIDS).

{168}{170} It is considered to be the treatment of choice for this indication. {94} Sulfamethoxazole and trimethoprim combination is indicated in both secondary prophylaxis (patients who own already had at least one episode of PCP), and primary prophylaxis (HIV-infected adults with a CD4 lymphocyte count less than or equal to 200 cells per cubic millimeter and/or less than 20% of entire lymphocytes; every children born to HIV-infected mothers, beginning at 4 to 6 weeks of age, and subsequent prophylaxis given as sure on the basis of age-specific CD4 lymphocyte count{94}) of PCP.

{03}{05}{53}{54}{55}{56}{57}{60}{61}{113}

Pneumonia, Pneumocystis carinii (treatment) —Oral and parenteral sulfamethoxazole and trimethoprim combinations are indicated as primary agents in the treatment of Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). {01}{03}{05}{18}{95}{168}{169}{170}{171}Pentamidine is considered an alternative agent for PCP.

Traveler’s diarrhea (treatment)—Oral sulfamethoxazole and trimethoprim combination is indicated in the treatment of traveler’s diarrhea caused by susceptible strains of enterotoxigenic Escherichia coli and Shigella species.

{03}{18}{38}{138}{139}{168}{170}

Urinary tract infections, bacterial (treatment)— Sulfadiazine and trimethoprim combination {150}{157}{158}{159}{160}{161}{162}{163}{164} and oral and parenteral sulfamethoxazole and trimethoprim combinations {01}{03}{22}{38}{140}{141}{168}{169}{170}{171} are indicated in the treatment of urinary tract infections caused by susceptible organisms.

[Biliary tract infections (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of biliary tract infections caused by susceptible organisms.

{38}

[Bone and joint infections (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of bone and joint infections caused by susceptible organisms. {22}{38}

[Chancroid (treatment)]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of chancroid. {38}{147}{148}{149}

[Chlamydial infections (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of chlamydial infections.

{37}

[Cyclospora infections (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of diarrhea caused by Cyclospora cayetanensis , but may not completely eradicate the organism. {106}{107}{108}{109}

[Endocarditis, bacterial (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of bacterial endocarditis caused by susceptible organisms. {37}{38}

[Gonorrhea, endocervical and urethral, uncomplicated (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of gonorrhea caused by susceptible organisms.

{22}{38}{146}

[Granuloma inguinale (treatment)]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of granuloma inguinale. {37}{145}

[HIV-related infections in Africa (prophylaxis)]1—Sulfamethoxazole and trimethoprim combination is used in the prophylaxis of HIV-related infections in Africa{172}{173}{174}.
—Given the large number of patients with HIV-related infections throughout Africa and the high mortality they experience, sulfamethoxazole and trimethoprim combination prophylaxis if widely applicable and implemented could significantly affect care and survival (i.e., could significantly lower morbidity and mortality) among HIV-infected patients in Africa{172}{173}{174}.

[Isosporiasis (prophylaxis and treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the prophylaxis and treatment of isosporiasis caused by Isospora belli .

{38}{39}{40}{104}

[Lymphogranuloma venereum (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of lymphogranuloma venereum. {38}{104}

[Meningitis (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of meningitis caused by susceptible organisms. {37}{38}

[Nocardiosis (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of nocardiosis. {22}{38}{104}{137}

[Paracoccidioidomycosis (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of paracoccidioidomycosis.

{38}

[Paratyphoid fever (treatment)] or
[Typhoid fever (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of paratyphoid and typhoid fevers caused by susceptible strains. {22}{38}

[Septicemia, bacterial (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of bacterial septicemia caused by susceptible organisms.

{37}{38}

[Sinusitis (treatment)]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of sinusitis caused by susceptible organisms. {38}{103}{104}

[Skin and soft tissue infections (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of skin and soft tissue infections, including burn wound infections caused by susceptible organisms.

{22}

[Toxoplasmosis (prophylaxis)]1—Sulfamethoxazole and trimethoprim combination is used in the primary prophylaxis of toxoplasmosis in patients with AIDS. {38}{94}{95}{100}{114}{115}{167}

[Urinary tract infections, bacterial (prophylaxis)]1—Sulfamethoxazole and trimethoprim combination is used in the prophylaxis of bacterial urinary tract infections. {37}{102}{142}

[Whipple’s disease (treatment)]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of Whipple’s disease.

What is a sulfa drug allergy

{104}{105}{109}{110}{111}{112}

—Not every strains of a specific organism may be susceptible to sulfonamide and trimethoprim combinations.

Unaccepted
Sulfamethoxazole and trimethoprim combination is not indicated for prophylaxis or prolonged therapy in otitis media. {03}{168}{170} Sulfamethoxazole and trimethoprim combination is not effective in the treatment of syphilis{37}{38} andUreaplasm urealyticum{37}.

Sulfamethoxazole and trimethoprim combination should not be used in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis since it may not eradicate streptococci and therefore may not prevent sequelae such as rheumatic fever.

{01}{05}{37}

1Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
Sulfadiazine: 250.28 {04}
Sulfamethoxazole: 253.28 {04}
Trimethoprim: 290.32 {04}

Mechanism of action/Effect:

Sulfonamides:

Sulfonamides are broad-spectrum, bacteriostatic anti-infectives. {22} They are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit a bacterial enzyme, dihydropteroate synthetase, that is responsible for incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid.

{23} This blocks the synthesis of dihydrofolic acid and decreases the quantity of metabolically athletic tetrahydrofolic acid, a cofactor for the synthesis of purines, thymidine, and DNA. {37}

Susceptible bacteria are those that must synthesize folic acid. Mammalian cells require preformed folic acid and cannot synthesize it.

What is a sulfa drug allergy

{37}{38} The action of sulfonamides is antagonized by PABA and its derivatives (e.g., procaine and tetracaine) and by the presence of pus or tissue breakdown products, which provide the necessary components for bacterial growth. {23}

Trimethoprim:

Trimethoprim is a bacteriostatic lipophilic feeble base structurally related to pyrimethamine. It binds to and reversibly inhibits the bacterial enzyme dihydrofolate reductase, selectively blocking conversion of dihydrofolic acid to its functional form, tetrahydrofolic acid.

{03}{22}{37} This depletes folate, an essential cofactor in the biosynthesis of nucleic acids, resulting in interference with bacterial nucleic acid and protein production. {23} Bacterial dihydrofolate reductase is approximately 50,000 to 100,000 times more tightly bound by trimethoprim than is the corresponding mammalian enzyme. {37}{38}

Trimethoprim exerts its effect at a step in the folate biosynthesis immediately subsequent to the one at which sulfonamides exert their effect. When trimethoprim is istered concurrently with sulfonamides, synergism occurs, which is attributed to inhibition of tetrahydrofolate production at 2 sequential steps in its biosynthesis.

{22}{23}{37}

Absorption:

Oral—Sulfonamides and trimethoprim are rapidly and well absorbed (70 to 100%). {22}{151}{152}

Distribution:

Sulfonamides:

Widely distributed throughout body tissues and fluids, including pleural {01}{23}{165}, peritoneal {01}{23}{165}, synovial {01}{23}{165}, middle ear {01}{23}, and ocular fluids {01}{23}{165}, as well as nasal secretions {154}, sputum {01}{23}, and prostate {152}, lymph {153}, and renal tissue {152}.

Sulfadiazine is distributed throughout entire body water {23}{37} and achieves higher concentrations in bile than does sulfamethoxazole {14}. Sulfonamides readily cross the placenta and are distributed into breast milk, also. {01}{23}{37} Sulfonamides penetrate into the cerebrospinal fluid (CSF) with CSF concentrations of sulfadiazine reaching 32 to 65% {151} and those of sulfamethoxazole reaching 14 to 30% of the corresponding blood concentrations.

{23}{27}{37}{38} Sulfonamides may be detected in the urine in approximately 30 minutes. {23}

Trimethoprim:

Rapidly and widely distributed to various tissues and fluids, including kidneys, liver, spleen, bronchial secretions, saliva, sputum, middle ear, and prostatic tissue and fluid.

What is a sulfa drug allergy

{01}{23}{37} Trimethoprim is also distributed into bile, aqueous humor, bone, mucosa, and seminal fluid. {37}{38} It penetrates into the CSF with CSF concentrations reaching 20 to 40% of corresponding plasma concentrations. {37}{38} Trimethoprim crosses the placenta and is distributed into breast milk. {01}{37}

Urine solubility:

Sulfadiazine: Acetylated sulfadiazine has the least solubility, followed by sulfadiazine.

{152}

Sulfamethoxazole: Acetylated sulfamethoxazole is more soluble than sulfadiazine, but less soluble than sulfamethoxazole. {152}

Vol D:

Sulfadiazine: Approximately 33.7 liters.

What is a sulfa drug allergy

{165}

Sulfamethoxazole: Approximately 0.21 liters per kg of body weight (L/kg). {23}{37}

Trimethoprim: Approximately 1.8 L/kg. {23}{37}

Protein binding:

Sulfonamides:

Sulfonamides compete with bilirubin for binding to albumin. Kernicterus may develop in premature infants or neonates. {37} Binding is decreased in patients with severely impaired renal function. {38} Only free, unbound drug has antibacterial activity. {27}

Sulfadiazine: Moderate (38 to 56%). {151}{152}

Sulfamethoxazole: Moderate to high (60 to 70%).

{01}{23}{38}

Trimethoprim:

Moderate (40 to 45%). {01}{23}{24}{37} Protein binding does not significantly decrease in patients with uremia. {38}

Biotransformation:

Sulfonamides—Hepatic; primarily by acetylation to inactive metabolites, which retain the toxicity of the parent compound. {23} Some hepatic glucuronide conjugation may happen. {37}

Trimethoprim—Hepatic; 10 to 20% metabolized to inactive metabolites by O-demethylation, ring N-oxidation, and alpha-hydroxylation; metabolites may be free or conjugated.

{24}

Half-life:

Sulfadiazine:

Normal renal function: 9 to 13.7 hours. {152}{155}{156}

Renal failure: Approximately 34 hours. {23}{38}

Sulfamethoxazole:

Normal renal function: 10 to 12 hours. {01}{03}{22}{23}{37}{38}

Creatinine clearance less than 10 mL per minute (mL/min) (0.17 mL per second [mL/sec]): 18 to 50 hours. {38}{118}

Trimethoprim:

Normal renal function: 8 to 10 hours. {01}{03}{22}{23}{24}{37}{152}{156}

Creatinine clearance less than 10 mL/min (0.17 mL/sec): Approximately 24 hours.

{38}{118}

Time to peak serum concentration

Oral:

Sulfadiazine: 2.7 to 4 hours. {152}{155}{156}

Sulfamethoxazole: 2 to 4 hours. {22}{23}

Trimethoprim: 1 to 4 hours. {03}{22}{23}{37}{38}{156}

Peak serum concentration:

Sulfadiazine:

Single 820-mg dose: 27.5 to 31.7 mcg/mL.

{152}{155}{156}

Sulfamethoxazole:

Oral, 800 mg twice a day: Approximately 40 mcg/mL. {23}{38}

Intravenous, 800 mg three times a day: Approximately 106 mcg/mL. {37}{38}

Trimethoprim:

Oral, 160 mg twice a day: Approximately 2 to 2.4 mcg/mL. {23}{38}{156}

Intravenous, 160 mg three times a day: Approximately 9 mcg/mL. {37}{38}

Elimination:

Sulfonamides—
Renal, by glomerular filtration, with some tubular secretion {01} and reabsorption of both athletic medication and metabolites.

Excretion is increased in alkaline urine {37}{38}.

Percent of medication unchanged in the urine—
Sulfadiazine: 43 to 58% in 24 hours. {151}{155}{156}
Sulfamethoxazole: 20 to 40%. {23}{37}

Little amounts are excreted in the feces, bile, and other body secretions. {38}

In dialysis—
Sulfamethoxazole is removed from the blood by hemodialysis. {21}{37} However, peritoneal dialysis is not effective. {27}{118}

Trimethoprim—
Renal, 40 to 60% excreted within 24 hours, primarily by glomerular filtration and tubular secretion {03}{22}{23}{37}{156}; of this quantity, 80 to 90% is excreted unchanged and the remainder is excreted as inactive metabolites.

{37} Excretion is increased in acid urine and decreased in alkaline urine. {38}
Little amounts are excreted in the feces and bile. {22}

In dialysis—
Significant amounts of trimethoprim are removed from the blood by hemodialysis {21}, requiring a full maintenance dose after dialysis. Peritoneal dialysis is not effective in removing trimethoprim from the blood. {118}

Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to sulfonamides or trimethoprim may be allergic to sulfonamide and trimethoprim combinations.

{01}{150}

Patients allergic to furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors may be allergic to sulfonamides also. {25}{26}

Patients sensitive to sulfites may own an allergic reaction to Bactrim I.V. since it contains sodium metabisulfite. {01}

Carcinogenicity

Sulfamethoxazole and trimethoprim—Long-term studies to assess the carcinogenic potential of sulfamethoxazole and trimethoprim combination own not been done.

{01}

Mutagenicity

Sulfamethoxazole and trimethoprim—Bacterial mutagenicity studies with sulfamethoxazole and trimethoprim combination own not been done. Trimethoprim has not been shown to be mutagenic in the Ames assay. Studies in human leukocytes cultured in vitro with sulfamethoxazole and trimethoprim combination, using concentrations that exceeded therapeutic serum concentrations, own not shown that sulfamethoxazole and trimethoprim combination causes chromosomal damage. {01}

Pregnancy/Reproduction
Fertility—
Sulfamethoxazole and trimethoprim: Studies in rats, given oral doses as high as 70 mg of trimethoprim per kg of body weight (mg/kg) and 350 mg/kg of sulfamethoxazole daily, own not shown that sulfamethoxazole or trimethoprim causes any adverse effects on fertility or general reproductive performance.

{01}

Pregnancy—
Sulfadiazine: FDA Pregnancy Category C. {151}

Sulfamethoxazole and trimethoprim: Sulfamethoxazole and trimethoprim cross the placenta.

What is a sulfa drug allergy

Adequate and well-controlled studies in humans own not been done. {01} However, prophylaxis for Pneumocystis carinii pneumonia (PCP) is recommended in HIV-infected pregnant women. {94} In one retrospective study in 186 women who received placebo or sulfamethoxazole and trimethoprim combination during pregnancy, the incidence of congenital abnormalities was lower (3.3% versus 4.5%) in the sulfamethoxazole and trimethoprim combination–treated group. No abnormalities were reported in the 10 children whose mothers received sulfamethoxazole and trimethoprim combination during the first trimester.

In another study, no congenital abnormalities were reported in 35 children whose mothers received sulfamethoxazole and trimethoprim combination at the time of conception or shortly thereafter. However, sulfamethoxazole and trimethoprim may interfere with folic acid metabolism in the fetus. {01}

Studies in rats given oral doses of 200 mg/kg of trimethoprim and 533 mg/kg of sulfamethoxazole own shown that sulfamethoxazole causes teratogenic effects (primarily cleft palates).

However, doses of 192 mg/kg of trimethoprim and 512 mg/kg of sulfamethoxazole, when istered separately, did not cause cleft palates in rats.

What is a sulfa drug allergy

Doses of 88 mg/kg of trimethoprim and 355 mg/kg of sulfamethoxazole own been shown to cause cleft palates when istered concurrently. {01} Studies in rabbits given doses of trimethoprim 6 times the usual human therapeutic dose own shown that trimethoprim causes an increase in the number of dead, resorbed, and malformed fetuses. {01}

FDA Pregnancy Category C. {01}

Labor and delivery—

Sulfonamides are not recommended at term since they may cause jaundice, hemolytic anemia, and kernicterus in the newborn.

{26}{38}

Breast-feeding

Sulfonamides—Sulfonamides are distributed into breast milk. {01} Use is not recommended in nursing women since sulfonamides may cause kernicterus in nursing infants. {01}{18}{150} Also, sulfonamides may cause hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD)–deficient infants. {26}

Trimethoprim—Trimethoprim is distributed into breast milk.

{01} Trimethoprim may interfere with folic acid metabolism in nursing infants.

Pediatrics

Sulfonamides compete for bilirubin binding sites on plasma albumin, increasing the risk of kernicterus in the newborn. Also, because the acetyltransferase system is not fully developed in the newborn, increased blood concentrations of the free sulfonamide can further increase the risk of kernicterus. {26}{38}

Sulfadiazine and trimethoprim:

Sulfadiazine and trimethoprim combination is not recommended in premature infants and neonates up to 12 weeks of age. {150}

Sulfamethoxazole and trimethoprim:

Although sulfamethoxazole and trimethoprim combination is indicated in the treatment of acute otitis media in children, it is not indicated for prophylaxis or prolonged therapy.

{03}

Except as concurrent adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis or for the prophylaxis of Pneumocystis carinii pneumonia (PCP) in infants 4 weeks of age or over, the use of sulfamethoxazole and trimethoprim combination is contraindicated in infants up to 2 months of age since sulfonamides may cause kernicterus in neonates. {18}{56}

Geriatrics

Elderly patients may be at increased risk of severe side/adverse effects. Severe skin reactions, generalized bone marrow depression, and decreased platelet count (with or without purpura) are the most frequently reported severe side/adverse effects in the elderly.

An increased incidence of thrombocytopenia with purpura has been reported in elderly patients who are receiving diuretics, primarily thiazides, concurrently with sulfonamide and trimethoprim combinations. {01}{18}{27}{150}

Pharmacogenetics
Sulfonamides are metabolized primarily by acetylation. {41} Patients can be divided into 2 groups, slow and quick acetylators. Slow acetylators own a higher incidence of severe sulfonamide reactions, although a slow acetylator phenotype is not thought to be the sole reason for sulfonamide toxicity.

{41}{42}{43}{44}{83} The incidence of the slow acetylator phenotype is approximately 50% in North American blacks and whites. {41}{42}{45}{83} Approximately 30% of the Hispanic population {43} and 10% of the Asian population {42} are slow acetylators. Also, acquired immunodeficiency syndrome (AIDS) patients with acute illness, but not AIDS patients who are stable or human immunodeficiency virus (HIV)-infected patients without AIDS, own an increased incidence of slow acetylation.

{43}

Dental

The leukopenic and thrombocytopenic effects of sulfonamides may result in an increased incidence of certain microbial infections, delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts own returned to normal. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Drug interactions and/or related problems
The following drug interactions and/or related problems own been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (»=major clinical significance):

Note:Combinations containing any of the following medications, depending on the quantity present, may also interact with this medication.

» Anticoagulants, coumarin- or indandione-derivative or {01}{47}{124}{125}{150}{168}{169}{170}{171}
» Anticonvulsants, hydantoin or {01}{47}{122}{150}{168}{169}{170}{171}
» Antidiabetic agents, oral {47}{120}{121}{150}{168}{170}{171}(these medications may be displaced from protein binding sites and/or their metabolism may be inhibited by some sulfonamides, resulting in increased or prolonged effects and/or toxicity; dosage adjustments may be necessary during and after sulfonamide therapy)

Atovaquone {149}(concurrent istration of sulfamethoxazole and trimethoprim combination with atovaquone suspension resulted in an 8 and 17% decrease in the steady-state serum concentration of sulfamethoxazole and trimethoprim, respectively; this effect is thought to be minor and is not expected to produce clinically significant events)

Bone marrow depressants (See Appendix II )(concurrent use of bone marrow depressants with sulfonamides may increase the leukopenic and/or thrombocytopenic effects; if concurrent use is required, shut observation for myelotoxic effects should be considered)

Contraceptives, estrogen-containing, oral {29}(concurrent long-term use of sulfonamides may result in reduced contraceptive reliability and increased incidence of breakthrough bleeding)

Cyclosporine {47}{48}{49}{50}{168}(concurrent use with sulfonamides may increase the metabolism of cyclosporine, resulting in decreased plasma concentrations and potential transplant rejection; there may also be additive nephrotoxicity; plasma cyclosporine concentrations and renal function should be monitored)

Dapsone {35}(concurrent use with trimethoprim will generally increase the plasma concentrations of both dapsone and trimethoprim, possibly due to an inhibition in dapsone metabolism, and/or competition for renal secretion between the 2 medications; increased serum dapsone concentrations may increase the number and severity of side effects, especially methemoglobinemia)

» Digoxin {168}(concurrent use with trimethoprim and sulfamethoxazole may increase the serum concentration of digoxin; serum digoxin levels should be monitored)

Folate antagonists, other (See Appendix II ) {150}(concurrent use with trimethoprim or use of trimethoprim between courses of other folic acid antagonists is not recommended because of the possibility of megaloblastic anemia)

» Hemolytics, other (See Appendix II )(concurrent use with sulfonamides may increase the potential for toxic side effects)

» Hepatotoxic medications, other (See Appendix II )(concurrent use with sulfonamides may result in an increased incidence of hepatotoxicity; patients, especially those on prolonged istration or those with a history of liver disease, should be carefully monitored)

Lamivudine (3TC)(in one little study, sulfamethoxazole and trimethoprim combination was found to decrease significantly the clearance, steady-state volume of distribution, and elimination half-life of lamivudine {36}; trimethoprim was also found to decrease the renal clearance of lamivudine by approximately 59% in an isolated perfused rat kidney {67})

» Methenamine {37}{38}(in acid urine, methenamine breaks below into formaldehyde, which may form an insoluble precipitate with certain sulfonamides and may also increase the harm of crystalluria; concurrent use is not recommended)

» Methotrexate or {01}{38}{51}{123}{150}{168}{169}{170}{171}
Phenylbutazone or {37}{38}{150}
Sulfinpyrazone {18}{38}{150}(the effect of methotrexate may be potentiated during concurrent use with sulfonamides because of displacement from plasma protein binding sites; phenylbutazone and sulfinpyrazone may displace sulfonamides from plasma protein-binding sites, increasing sulfonamide concentrations)

Procainamide {31}{32}(concurrent use with trimethoprim may increase the plasma concentration of both procainamide and its metabolite, N-acetylprocainamide [NAPA], by decreasing their renal clearance)

Rifampin {30}{38}(concurrent use may significantly increase the elimination and shorten the elimination half-life of trimethoprim)

Thiazide diuretics {01}(there has been an increased incidence of thrombocytopenia with purpura in elderly patients who received sulfamethoxazole and trimethoprim combination with thiazide diuretics)

Tricyclic antidepressants(efficacy of tricyclic antidepressants may be decreased)

Laboratory worth alterations
The following own been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (»=major clinical significance):

With diagnostic test results
Benedict»s test {37}{52}(sulfonamides may produce a false-positive Benedict»s test for urine glucose )

Creatinine determinations {01}{18}{168}(trimethoprim may interfere with the Jaffé alkaline picrate assay for creatinine, resulting in creatinine values that are approximately 10% higher than actual values)

Methotrexate assays, serum {01}{18}{168}{169}(trimethoprim may interfere with serum methotrexate assays if methotrexate is measured by the competitive binding protein technique [CBPA] using a bacterial dihydrofolate reductase as the binding protein; no interference occurs if methotrexate is measured by radioimmunoassay [RIA])

Sulfosalicylic acid test {37}{52}(sulfonamides may produce a false-positive sulfosalicylic acid test for urine protein)

Urine urobilinogen test strip (e.g., Urobilistix) {37}{52}(sulfonamides may interfere with the Urobilistix test for urinary urobilinogen )

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) values, serum and
Aspartate aminotransferase (AST [SGOT]) values, serum and
Bilirubin, serum(concentrations may be increased {01}{18}{66}{150})

Blood urea nitrogen (BUN) and
Creatinine, serum(concentrations may be increased {01}{37}{49}{66})

Glucose, blood(concentrations may be decreased, resulting in hypoglycemia on rare occasions {65})

Potassium, serum(concentrations may be increased; this generally occurs with higher doses, such as for the treatment of Pneumocystis carinii pneumonia, but may also happen at regular doses {76}{77}{78}{79}{80}{81})

Medical considerations/Contraindications
The medical considerations/contraindications included own been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (»=major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problem exists:
» Allergy to sulfonamides, furosemide, thiazide diuretics, sulfonylureas, carbonic anhydrase inhibitors, sulfites, or trimethoprim {01}{18}
Risk-benefit should be considered when the following medical problems exist
» Blood dyscrasias or
» Megaloblastic anemia due to folate deficiency {01}{24}{27}{168}{169}{170}{171}(trimethoprim may cause folic acid deficiency; sulfonamides and trimethoprim may cause blood dyscrasias)

» Glucose-6-phosphate dehydrogenase (G6PD) deficiency {01}{37}{116}{117}{150}{168}{169}{170}{171}(hemolysis may rarely occur; frequency may be dose-related)

» Hepatic function impairment {01}{21}{150}{168}{169}{170}{171}(sulfonamides and trimethoprim are metabolized in the liver; delayed metabolism may increase the risk of toxicity; also, sulfonamides may cause fulminant hepatic necrosis)

» Porphyria {26}{28}(sulfonamides may precipitate an acute attack of porphyria)

» Renal function impairment {01}{21}{27}{150}{168}{169}{170}{171}(sulfonamides and trimethoprim are renally excreted; delayed elimination may increase the risk of toxicity; sulfonamides may cause tubular necrosis or interstitial nephritis)

Patient monitoring
The following may be especially significant in patient monitoring (other tests may be warranted in some patients, depending on condition; »=major clinical significance):

Finish blood counts (CBCs) {01}{27}{150}{168}{169}{170}{171}(may be required prior to and monthly during treatment to detect blood dyscrasias in patients on prolonged therapy; therapy should be discontinued if a significant decrease in the count of any formed blood elements occurs)

Urinalyses {01}{27}{150}{168}{169}{170}{171}(may be required prior to and periodically during treatment to detect crystalluria and/or urinary calculi formation in patients on long-term or high-dose therapy and in patients with impaired renal function)

Side/Adverse Effects

Note:Fatalities own occurred, although rarely, due to severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.

Therapy should be discontinued at the first appearance of skin rash or any serious side/adverse effects or if signs of folic acid deficiency happen. {01}{18}{168}{169}{170}{171}
Patients infected with human immunodeficiency virus (HIV) own a greater incidence of side/adverse effects, especially rash, fever, and leukopenia, than do non-HIV–infected patients. {01}{85}{86}{168}{169}{170}{171} On rare occasions, adverse reactions may become extremely severe or life-threatening.

{85}{86}{87}{88} Adverse effects may happen in up to 65% of acquired immunodeficiency syndrome (AIDS) patients {66}{84}, with 24 to 57% having such severe toxicity that therapy has to be discontinued. {66} Sulfamethoxazole and trimethoprim combination desensitization in HIV-infected patients has been successful in some patients, who own then been capable to tolerate regular dosing for the prophylaxis of Pneumocystis carinii pneumonia (see Selected Bibliography).

What is a sulfa drug allergy

{89}{90}{91}{92}{93}{166}
The multiorgan toxicity of sulfonamides is thought to be the result of the way sulfonamides are metabolized in certain patients. It is probably due to the inability of the body to detoxify reactive metabolites. Sulfonamides are metabolized primarily by acetylation. {41}{83}{135} Patients can be divided into slow and quick acetylators. Slow acetylation of sulfonamides makes more of the medication available for metabolism by the oxidative pathways of the cytochrome P-450 system. {44}{45}{83} These pathways produce reactive toxic metabolites, such as hydroxylamine and nitroso compounds.

{43}{44}{45}{135} The metabolites are normally detoxified by scavengers, such as glutathione. However, some populations, such as HIV-infected patients, own low concentrations of glutathione and these metabolites accumulate, producing toxicity. {43}{46}{83}{135} Patients who are slow acetylators own a higher incidence of sulfonamide hypersensitivity reactions {41}{42}{43}{44}, although severe toxicity has also been seen in quick acetylators.

{41} Acetylation status alone cannot fully explain sulfonamide toxicity {45}{83} since approximately 50% of North American blacks and whites are slow acetylators and severe reactions happen in less than 1% of patients treated with sulfonamides. {45} However, decreased acetylation may increase the quantity of sulfonamide metabolized to toxic metabolites. {45}{135}
Sulfonamides own been associated with crystalluria in the past; however, the risk is little with current sulfonamides and the doses used.

Acetylated sulfadiazine has the least solubility, followed by sulfadiazine, acetylated sulfamethoxazole, and sulfamethoxazole. {152} Solubility also varies with pH and dose. The risk of crystalluria is high with sulfadiazine at a combined dose of 6 grams a day (4920 mg of sulfadiazine and 1080 mg of trimethoprim); however, this is 6 times the recommended daily dose. {152}

The following side/adverse effects own been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent

Hypersensitivity (fever; itching; skin rash){01}{18}{37}{66}

photosensitivity (increased sensitivity of skin to sunlight){01}{18}{37}

Incidence less frequent

Blood dyscrasias (fever and sore throat; pale skin; unusual bleeding or bruising; unusual tiredness or weakness){01}{18}{23}{59}{66}{133}{134}{150}{168}{169}{170}{171}

cholestatic hepatitis (yellow eyes or skin ){01}{68}{69}{70}{71}{129}{130}{150}{168}{169}{170}{171}

pancreatitis (back or stomach pain, severe; quick heart beat; fever; nausea or vomiting; swelling of the stomach){168}{169}{170}{171}

Stevens-Johnson syndrome (aching joints and muscles; redness, blistering, peeling, or loosening of skin; unusual tiredness or weakness){01}{18}{23}{37}{150}{168}{169}{170}{171}

toxic epidermal necrolysis ( difficulty in swallowing; redness, blistering, peeling, or loosening of skin){01}{18}{23}{37}{150}{168}{169}{170}{171}

Incidence rare

Aseptic meningitis (confusion; drowsiness; general feeling of illness; severe headache; nausea; stiff neck and/or back){01}{33}{34}{72}{73}{74}{75}{131}{132}{168}{169}{170}{171}

central nervous system (CNS) toxicity (anxiety; hallucinations; mental depression; nervousness; seizures (convulsions)){01}{126}{127}{128}{150}{168}{169}{170}{171}

Clostridium difficile colitis ( severe abdominal or stomach cramps and pain; abdominal tenderness ; watery and severe diarrhea, which may also be bloody; fever)—may happen up to several weeks after discontinuation of medication{01}{82}{136}

crystalluria or hematuria (blood in urine ; lower back pain; pain or burning while urinating){01}{152}

goiter or thyroid function disturbance ( swelling of front part of neck){01}{37}

interstitial nephritis or tubular necrosis (greatly increased or decreased frequency of urination or quantity of urine; increased thirst; loss of appetite ; nausea; vomiting){01}{37}{150}{168}{169}{170}{171}

methemoglobinemia (bluish fingernails, lips, or skin; hard breathing; pale skin; sore throat and fever; unusual bleeding or bruising; unusual tiredness or weakness){01}{37}{168}{169}{170}{171}

rhabdomyolysis ( fatigue; muscle pain; muscle weakness)—has been reported mainly in AIDS patients

thrombophlebitis (pain at site of injection){01}{37}

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent

CNS effects (dizziness; headache; ringing in the ears; tiredness){01}{23}{37}{150}

gastrointestinal disturbances (abdominal pain ; diarrhea; loss of appetite; nausea or vomiting){01}{18}{23}{37}{66}{150}

glossitis or stomatitis (mouth sores; swelling of the tongue){168}{169}{170}{171}

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sulfonamides and Trimethoprim (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
» Conditions affecting use, especially:
Allergy to sulfonamides, furosemide, thiazide diuretics, sulfonylureas, carbonic anhydrase inhibitors, sulfites, or trimethoprim

Pregnancy—Sulfonamides and trimethoprim cross the placenta; trimethoprim may interfere with folic acid metabolism; use is not recommended at term since sulfonamides may cause jaundice, hemolytic anemia, and kernicterus in neonates

Breast-feeding—Sulfonamides and trimethoprim are distributed into breast milk; sulfonamides may cause kernicterus in nursing infants; trimethoprim may interfere with folic acid metabolism

Use in children—Sulfadiazine and trimethoprim combination is contraindicated in infants up to 3 months of age and sulfamethoxazole and trimethoprim combination is contraindicated in infants up to 2 months of age for most indications since sulfonamides may cause kernicterus in neonates; however, sulfamethoxazole and trimethoprim combination is indicated in every infants born to human immunodeficiency virus (HIV)–infected mothers, starting at 4 to 6 weeks

Use in the elderly—Elderly patients, especially those also taking diuretics, may be at increased risk of severe side/adverse effects
Other medications, especially coumarin- or indandione-derivative anticoagulants, hydantoin anticonvulsants, oral antidiabetic agents, other hemolytics, other hepatotoxic medications, methenamine, or methotrexate
Other medical problems, especially blood dyscrasias, G6PD deficiency, hepatic function impairment, megaloblastic anemia due to folic acid deficiency, porphyria, and renal function impairment

Proper use of this medication
» Not giving sulfadiazine and trimethoprim combination to infants under 3 months of age, or sulfamethoxazole and trimethoprim combination to infants under 2 months of age, except under special circumstances

» Maintaining adequate fluid intake

Proper istration technique for oral liquids

» Compliance with full course of therapy

» Importance of not missing doses and taking at evenly spaced times

» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Regular visits to physician to check blood counts

Checking with physician if no improvement within a few days

Caution in use of regular toothbrushes, dental floss, and toothpicks; deferring dental work until blood counts own returned to normal; checking with physician or dentist concerning proper oral hygiene

» Possible skin photosensitivity

» Caution if dizziness occurs

Side/adverse effects
Severe skin problems and blood problems may be more likely to happen in elderly patients who are taking sulfamethoxazole and trimethoprim combination, especially if diuretics are being taken concurrently

Signs of potential side effects, especially hypersensitivity, photosensitivity, blood dyscrasias, cholestatic hepatitis, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, aseptic meningitis, central nervous system toxicity, Clostridium difficile colitis, crystalluria, hematuria, goiter, thyroid function disturbance, interstitial nephritis, tubular necrosis, methemoglobinemia, rhabdomyolysis and thrombophlebitis

General Dosing Information
Fluid intake should be sufficient to maintain urine output of at least 1200 mL per day in adults.

{05}{18}

Adults with renal function impairment require a reduction in dose in sulfonamide and trimethoprim combinations as follows: {01}{150}

SULFADIAZINE AND TRIMETHOPRIM

Summary of Differences
Indications: Sulfadiazine and trimethoprim combination is recommended for use only in the treatment of urinary tract infections.

Pharmacology/pharmacokinetics: Compared to sulfamethoxazole, sulfadiazine achieves higher concentrations in the bile and cerebrospinal fluid, is metabolized to a lesser extent, and a higher percentage of athletic medication is eliminated in the urine. {14}{23}{37}{151}{152}{155}{156}{165}

Additional Dosing Information
The usual length of therapy when treating an uncomplicated lower urinary tract infection with sulfadiazine and trimethoprim combination is three {157}{159}{160} to five {158} days in women and seven to ten days in men {64}.

Therapy should be continued for fourteen days or more in upper urinary tract infections. {64}

Oral Dosage Forms

SULFADIAZINE AND TRIMETHOPRIM ORAL SUSPENSION

Usual adult and adolescent dose
Antibacterial
Oral, 820 mg of sulfadiazine and 180 mg of trimethoprim once a day. {150}

Usual pediatric dose
Antibacterial
Infants up to 3 months of age: Use is not recommended. {150}

Children 3 months to 12 years of age: Oral, 7 mg of sulfadiazine and 1.5 mg of trimethoprim per kg of body weight every twelve hours.

{150}

Children over 12 years of age: See Usual adult and adolescent dose.{150}

Strength(s) generally available
U.S.—
Not commercially available.

Canada—

205 mg of sulfadiazine and 45 mg of trimethoprim per 5 mL (Rx) [Coptin]

Packaging and storage:
Store under 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
• Shake well.
• Take with a full glass of water.
• May cause dizziness.
• Avoid too much sun or use of sunlamp.
• Continue medicine for full time of treatment.

Note:When dispensing, include a calibrated liquid-measuring device.

SULFADIAZINE AND TRIMETHOPRIM TABLETS

Usual adult and adolescent dose
See Sulfadiazine and Trimethoprim Oral Suspension .

{150}

Usual pediatric dose
See Sulfadiazine and Trimethoprim Oral Suspension . {150}

Strength(s) generally available
U.S.—
Not commercially available.

Canada—

410 mg of sulfadiazine and 90 mg of trimethoprim (Rx) [Coptin]

820 mg of sulfadiazine and 180 mg of trimethoprim (Rx) [Coptin 1]

Packaging and storage:
Store under 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
• Take with a full glass of water.
• May cause dizziness.
• Avoid too much sun or use of sunlamp.
• Continue medicine for full time of treatment.

SULFAMETHOXAZOLE AND TRIMETHOPRIM

Summary of Differences
Pharmacology/pharmacokinetics: Sulfamethoxazole is more soluble in urine than is sulfadiazine.

{152}

Additional Dosing Information
Therapy should be continued for at least ten to fourteen days in acute exacerbations of chronic bronchitis {05}; as single-dose therapy or for three to five {119} days in urinary tract infections {101}{140}{141}{143}{144}; for five {05} to seven {119} days in shigellosis; for ten days in acute otitis media in children {05}; for five days in travelers diarrhea {05}; and for fourteen to twenty-one days in Pneumocystis carinii pneumonia {05}.

Sulfamethoxazole and trimethoprim combination may also be given for one or two days or as single-dose therapy for lower urinary tract infections. Therapy should be continued for fourteen days or more in upper urinary tract infections. {64}

Oral Dosage Forms

Note:Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

SULFAMETHOXAZOLE AND TRIMETHOPRIM ORAL SUSPENSION USP

Usual adult and adolescent dose
Antibacterial (systemic)
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim every twelve hours.

{03}{05}

Antiprotozoal

Pneumocystis carinii pneumonia {03}:

Treatment—
Oral, 18.75 to 25 mg of sulfamethoxazole and 3.75 to 5 mg of trimethoprim per kg of body weight every six hours for fourteen to twenty-one days {03}{05}{168}{169}{170}{171}.

Prophylaxis1
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day. {05}{94}{97}{98}{99}{168}{170}

Acceptable alternative dosing schedules include—
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim three times a week (e.g., Monday, Wednesday, Friday) {55}{62}{63}{94}.

Oral, 400 mg of sulfamethoxazole and 80 mg of trimethoprim once a day {94}{96}{99}.

[Toxoplasmosis (prophylaxis)]1:
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day.

{94}

Acceptable alternative dosing schedules include—
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim three times a week (e.g., Monday, Wednesday, Friday) {94}.

Oral, 400 mg of sulfamethoxazole and 80 mg of trimethoprim once a day. {94}

[ HIV-related infection in Africa (prophylaxis)]1
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day{172}{173}{174}.

Usual pediatric dose
Antibacterial (systemic)

Infants up to 2 months of age:
Use is not recommended since sulfonamides may cause kernicterus in neonates.

{03}{168}{169}{170}{171}

Infants 2 months of age and over:
Infants and children up to 40 kg of body weight—Oral, 20{168}{170} to 30 mg of sulfamethoxazole and 4 {168}{170}to 6 mg of trimethoprim per kg of body weight every twelve hours. {03}{58}

Children 40 kg of body weight and over—See Usual adult and adolescent dose.

Antiprotozoal

Sulfa allergy is a term used to describe an adverse drug reaction to sulfonamides, a class of drugs that includes both antibiotics and non-antibiotics.

Ideally, a physician will document what specific sulfa drug was associated with what specific reaction as the term "sulfa allergy" alone may unnecessarily lead to avoidance of drugs that may be tolerated.

There's a common misconception that every sulfonamide drugs are equally likely to cause an allergic or adverse reaction, but this isn't true.

(All drugs own the potential to cause allergy.) Antibiotic sulfonamides (used to treat bacterial infections) are more likely to trigger an allergic reaction than nonantibiotic ones.

While every drugs own the potential to cause an allergy, non-antibiotic sulfonamides are less likely sources.


Diagnosis

There's no validated skin or blood test available to diagnose a sulfa allergy. The diagnosis is generally made on careful review of the suspected reaction and history of current and previous medication use.


Treatment

The first-line of treatment of a sulfa allergy is typically the termination of the suspected drug.

Anaphylaxis requires immediate epinephrine use and medical care.

Stevens-Johnson syndrome or toxic epidermal necrolysis are also potentially life-threatening conditions that require immediate medical evaluation; in severe cases, management in a burn unit may be required.

In milder cases where a sulfa drug is considered essential to the treatment of an infection, an allergist or other qualified physician may supervise the istration of smaller doses and gradually increase them as the drug is better tolerated.


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