Conray 43

For all uses of Conray 43 (iothalamate meglumine):

• If you have an allergy to iothalamate meglumine or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are dehydrated, have been eating poorly, or have used a laxative or water pill before Conray 43.
• If you have had a skin reaction to this medicine or another drug like it in the past.
• If you are taking metformin, talk with doctor.
• If you are breast-feeding. Do not breast-feed for 24 hours after getting Conray 43.

If used before an x-ray of a joint:

• If you have an infection in or near the joint being x-rayed.

If used before an x-ray of the liver or bile duct:

• If you have a blood clotting problem, talk with your doctor.

If used before an endoscopy:

• If you have pancreatitis, talk with your doctor.
• If you have a certain bile duct problem (cholangitis).

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Conray 43 with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Very bad health problems, paralysis, and death have happened when contrast has been given into blood vessels in the spinal cord. Talk with the doctor.
• Very bad and sometimes deadly allergic reactions have rarely happened. Talk with your doctor.
• Blood clots have happened with Conray 43 when used with some heart procedures. Sometimes, blood clots may cause heart attack and stroke, which may be deadly. Talk with the doctor.
• Seizures and death have happened when contrast has been given to people with bleeding in the brain. Talk with the doctor.
• Very bad kidney problems and sometimes death have happened when contrast has been given to people with multiple myeloma. Talk with the doctor.
• Thyroid problems have happened after use of this medicine. Some people had to be treated for these thyroid problems. Talk with the doctor.
• A very bad and sometimes deadly reaction has happened with Conray 43. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• If you have sickle cell disease, talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• If you are 65 or older, use Conray 43 with care. You could have more side effects.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Use Conray 43 (iothalamate meglumine) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• This medicine is given as a shot into a vein or artery only.
• Other drugs may be given before this medicine to help avoid side effects.
• You will need to be sure that you are not dehydrated before getting Conray 43. Check with your doctor to see if you need to drink extra fluids before getting this medicine.
• Drink lots of noncaffeine liquids after using Conray 43 unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Sneezing.
• Stuffy nose.
• Cough.
• Choking.
• Shortness of breath.
• Blue or gray skin color.
• Chest pain or pressure or a fast heartbeat.
• A heartbeat that does not feel normal.
• Very bad dizziness or passing out.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Seizures.
• This medicine may cause tissue damage if the drug leaks from the vein. Tell your nurse if you have any redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into your body.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Conray 43 should not be used for myelography.

Refer to PRECAUTIONS, General, concerning hypersensitivity.

Contraindications to the procedure of retrograde pyelography include obstruction to endoscopy or catheterization of the ureters, severe systemic disease which contraindicates instrumentation and acute infection of the upper urinary tract.

SEVERE ADVERSE EVENTS – INADVERTENT INTRATHECAL ADMINISTRATION:

Serious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use. These serious adverse reactions include: death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to ensure that this drug product is not administered intrathecally.

Ionic iodinated contrast media inhibit blood coagulation, in vitro, more than nonionic contrast media. Nonetheless, it is prudent to avoid prolonged contact of blood with syringes containing ionic contrast media.

Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state and concomitant medications may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to guidewire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinized saline solutions and minimizing the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.

Serious or fatal reactions have been associated with the administration of iodine containing radiopaque media. It is of utmost importance to be completely prepared to treat any contrast medium reaction.

Serious neurologic sequelae, including permanent paralysis, have been reported following cerebral arteriography, selective spinal arteriography and arteriography of vessels supplying the spinal cord. The intravascular injection of a contrast medium should never be made following the administration of vasopressors since they strongly potentiate neurologic effects.

In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinical deterioration, including convulsions and death, has been reported. Therefore, administration of intravascular iodinated ionic contrast media in these patients should be undertaken with caution.

A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma.  In such instances anuria has developed resulting in progressive uremia, renal failure and eventually death. Although neither the contrast agent nor dehydration has separately proved to be the cause of anuria in myeloma, it has been speculated that the combination of both may be causative factors. The risk in myelomatous patients is not a contraindication to the procedure; however, partial dehydration in the preparation of these patients for the examination is not recommended since this may predispose to precipitation of myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing the effect. Myeloma, which occurs most commonly in persons over 40, should be considered before instituting intravascular administration of contrast agents.

Administration of radiopaque materials to patients known or suspected to have pheochromocytoma should be performed with extreme caution.  If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure, and measures for treatment of a hypertensive crisis should be available.

Contrast media have been shown to promote the phenomenon of sickling in individuals who are homozygous for sickle cell disease when the material is injected intravenously or intra-arterially.

Convulsions have occurred in patients with primary or metastatic cerebral lesions following the administration of iodine-containing radiopaque media for the contrast enhancement of CT brain images.

In patients with advanced renal disease, iodinated contrast media should be used with caution, and only when the need for the examination dictates, since excretion of the medium may be impaired. Patients with combined renal and hepatic disease, those with severe hypertension or congestive heart failure, and recent renal transplant recipients may present an additional risk.

Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with occult renal disease, notably diabetics and hypertensives. In these classes of patients there should be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment.

Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible non-diabetic patients (often elderly with pre-existing renal disease) following the administration of iodinated contrast agents. Therefore, careful consideration of the potential risks should be given before performing this radiographic procedure in these patients.

Caution should be exercised in performing contrast medium studies in patients with endotoxemia and/or those with elevated body temperatures.

Reports of thyroid storm occurring following the intravascular use of iodinated radiopaque agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest that this additional risk be evaluated in such patients before use of this drug. Iodine containing contrast agents may alter the results of thyroid function tests which depend on iodine estimation, e.g. PBI and radioactive iodine uptake studies. Such tests, if indicated, should be performed prior to the administration of this preparation.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Conray 43 to patients with a history of a severe cutaneous adverse reaction to Conray 43.

Intravascular Procedures

Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and idiosyncratic reactions.

Chemotoxic reactions result from the physio-chemical properties of the contrast media, the dose and speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by the contrast medium are included in this category.

Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40 years old. Idiosyncratic reactions may or may not be dependent on the amount of dose injected, the speed of injection, the mode of injection and the radiographic procedure. Idiosyncratic reactions are subdivided into minor, intermediate and severe. The minor reactions are self-limited and of short duration; the severe reactions are life-threatening and treatment is urgent and mandatory.

Fatalities have been reported following the administration of iodine-containing contrast agents. Based upon clinical literature, the incidence of death is reported to range from one in 10,000 (0.01 percent) to less than one in 100,000 (0.001 percent).

The following adverse reactions have been observed in conjunction with the use of iodine-containing contrast agents.

The most frequent  adverse reactions are nausea, vomiting, facial flush and a feeling of body warmth. These are usually of brief duration. Other reactions include the following:

Hypersensitivity reactions:   Dermal manifestations of urticaria with or without pruritus, erythema and maculopapular rash. Dry mouth. Sweating. Conjunctival symptoms. Facial, peripheral and angioneurotic edema. Symptoms related to the respiratory system include sneezing, nasal stuffiness, coughing, choking, dyspnea, chest tightness and wheezing, which may be initial manifestations of more severe and infrequent reactions including asthmatic attack, laryngospasm and bronchospasm with or without edema, pulmonary edema, apnea and cyanosis. Rarely, these allergic-type reactions can progress into anaphylaxis with loss of consciousness and coma and severe cardiovascular disturbances.

Cardiovascular reactions:  Generalized vasodilation, flushing and venospasm. Occasionally, thrombosis or rarely, thrombophlebitis. Red blood cell clumping and agglutination, crenation and interference in clot formation. Extremely rare cases of disseminated intravascular coagulation resulting in death have been reported. Severe cardiovascular responses include rare cases of hypotensive shock, coronary insufficiency, cardiac arrhythmia, fibrillation and arrest. These severe reactions are usually reversible with prompt and appropriate management; however, fatalities have occurred.

Endocrine reactions: Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to adult and pediatric patients, including infants. Some patients were treated for hypothyroidism.

Skin and Subcutaneous Tissue Disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticaria and skin discoloration) to severe: [Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)].

Technique reactions:   Extravasation with burning pain, hematomas, ecchymosis and tissue necrosis, paresthesia or numbness, vascular constriction due to injection rate, thrombosis and thrombophlebitis.

Neurological reactions:   Spasm, convulsions, aphasia, syncope, paresis, paralysis resulting from spinal cord injury and pathology associated with syndrome of transverse myelitis, visual field losses which are usually transient but may be permanent, coma and death.

Other reactions:   Headache, trembling, shaking, chills without fever and lightheadedness. Temporary renal shutdown or other nephropathy.

(Adverse reactions to specific procedures receive comment under that procedure.)

Retrograde Urographic Procedures

Irritation of the bladder or ureter, common to some degree to all contrast media administered for retrograde urographic procedures, may occasionally occur.

As with all contrast media, intravasation may lead to hypersensitivity reactions such as a sense of warmth, flushing, sneezing, sweating, chills, fever, urticaria, laryngeal edema, bronchospasm, hypertension, hypotension, cardiac arrhythmias and cardiac arrest.

Oliguria or anuria may occur following retrograde pyelography, especially in patients with severe pre-existing renal disease.

Adverse reactions associated with procedural technique include injury to the urethra, bladder, ureter, and introduction of infection.

In the event of serious or anaphylactoid reactions, it should be kept in mind that the reactions known to occur with intravenous administration of radiopaque contrast materials are possible.

Arterial digital subtraction angiography provides images similar in quality to conventional film-screen systems. The advantages of arterial DSA when compared to standard film angiography include the use of less contrast medium; the use of a lower concentration of contrast medium as provided by Conray 43; a decreased need for selective arterial catheterization and a shortened examination time. The limitations of arterial DSA include: reduced spatial resolution and limited field size.

Patient Preparation

No special patient preparation is required for arterial DSA. However, it is advisable to ensure that patients are well hydrated prior to examination.

Precautions

In addition to the general precautions described, the risks associated with arterial DSA are those usually attendant with catheter procedures. Following the procedure, gentle pressure hemostasis is required, followed by observation and immobilization of the limb for several hours to prevent hemorrhage from the site of arterial puncture.

Usual Dosage

It is advisable to inject at rates approximately equal to the flow rate of the vessel being injected. The following volumes per injection, have been used, and may be repeated as necessary:

Carotid or Vertebral Arteries                               3-10 mL
Aortic Arch                                                       15-30 mL
Subclavian and Brachial Arteries                          5-15 mL
Major branches of the Aorta                                5-30 mL
Abdominal Aorta                                               10-30 mL

A total dose of 200 mL (representing 40.4 grams of iodine) should not be exceeded. Consideration should be given to the patient's clinical condition and whether large volumes of fluids may be detrimental to patient care.

Retrograde Urographic Administration

Unless contraindicated, an appropriate laxative is given the night before the examination.

The radiographic procedure normally employed for cystography, cystourethrography and retrograde pyelography should be employed. A preliminary radiograph is recommended before the contrast agent is administered.

Sterile catherization is essential. Conray 43 may be introduced by gravity flow using an appropriate venoclysis set or by syringe. Excessive pressure should be avoided with any method of administration.

Retrograde Pyelography  – Ordinarily about 25 mL of Conray 43 are required for bilateral and 15 mL for unilateral pyelograms. About 5 to 6 mL are usually administered for each exposure. Children usually require a volume reduced in proportion to their body size.

Cystography and Cystourethrography – Either Conray 43 supplied at 43% w/v concentration of iothalamate meglumine or Cysto-Conray II supplied at a 17.2% w/v concentration of iothalamate meglumine may be used for these procedures. (SEE CYSTO-CONRAY II PACKAGE INSERT FOR SPECIFIC INFORMATION ABOUT THE USE OF THIS PRODUCT.) The desired concentration will vary depending upon the patient's size and age and also with the technique and equipment used. Sufficient volume of contrast medium is administered to adequately fill the urinary bladder. The volume of solution required will vary depending upon the individual patient. Adults usually require a volume in the range of 200 to 400 mL. Children require a volume in proportion to their body size. The usual dose ranges from 30 to 300 mL.