Gadolinium is a periodic table element that possesses high-end metallurgic properties, something that is used extensively in nuclear reactors and radiography. Gadolinium is not known to have any biological roles; however, with technical and medicinal research taking the center point of research and commercial application, Gadolinium’s use in the spectrum of medical synthesis is being utilized and tested considerably. Gadolinium on its own is highly toxic but its usage in biomedicine has a permissible limit for quantitative use.

Prescription Name and Overview

The utility of gadolinium in the contemporary scope of biomedicine has found some beneficial and effective advantages. The most important use of the element along the lines of human diagnosis is during MRIs, MRAs and CT Scan for defined radiology insight. Gadolinium-Based Contrast Agents or GBCAs are injected in patients undergoing the above mentioned diagnostic tests. Its use has been modified and experimented especially in electrophysiology that helps in the detection of various cardiovascular disparities. 

There have reported cases of gadolinium toxicity in patients but permissible amounts of GBCAs are accepted with wide-spread affirmation in medical diagnostics. GBCAs are categorized into two concrete types namely, macrocyclic and linear. There are many manufacturing names under these two categorizations that are prescribed as per the test modules. Some FDA approved GBCA products under linear GBCA include Magnevist, Eovist, MultiHance, Omniscan, OptiMARK, and Ablavar. On the other hand, macrocyclic GBCA products include Dotarem, ProHance, and Gadavist as usable products in the scope of medicinal detection.

Generic Name and Overview

The generic nomenclature of GBCAs again branches out into the two types: macrocyclic and linear. Every GBCA product with a prescription name has its lateral generic name under its usability and bio-distribution categories. Say, for example, the generic name for Omniscan is Gadodiamide whereas, for ProHance, the generic name is Gadoteridol. Likewise, every manufactured product name has its own generic nomenclature. 

Generic Name                                               Prescription Name

Gadodiamide                                                   Omniscan

Gadoversetamide                                           Optimark

Gadopentetate dimeglumine                       Magnevist

Gadobenate dimeglumine                             MultiHance

Gadoxetate disodium                                     Eovist/Primovist

Gadofosveset trisodium                                 Ablavar/Vasovist

Gadoterate meglumine                                  Dotarem

Gadobutrol                                                       Gadavist/Gadovist

Gadoteridol                                                      ProHance

OTC Name and Overview

        Manufacturer

Gadolinium-Based Contrast Agent products are released under many medical manufacturers. Each product has its own manufacturer in terms of commercial production and use. For example, linear GBCA product Omniscan is manufactured by GE Healthcare whereas macrocyclic GBCA Dotarem is manufactured by Guerbet LLC. Likewise, every categorized GBCA product has its own manufacturing company for distribution as a commercial product of use.

The use of gadolinium in medical science has come a long way of sustainable experimentation and scientific development and its use in practical medication and diagnostic are indeed revolutionary. Structural difference in GBCA products categorizes them into linear and macrocyclic products. Now each product has its own manufacturing brands that sell them for commercial, medical use. Some of these manufacturers of GBCA products include:

• Bracco Diagnostics Inc.
• GE Healthcare
• Liebel-Flarsheim Company LLC
• Lantheus Medical Imaging, Inc.
• Guerbet LLC
• Bracco Diagnostics
• Bayer HealthCare Pharmaceuticals Inc.

          Labeled Indications

• Gadolinium by far has no use in biology but induces toxicity if used in higher amounts. 
• Gadolinium, in its elemental form, has no use of its own but its compounds known as Gadolinium-Based Contrast Agent products are used extensively as research tools in bioscience and biomedicine. 
• Improving the visibility of the internal structures of the human body during resonance imaging or MRI, these chelated compounds form the basic components of its contrast agents. 
• Another major use of Gadolinium is in ion channel electrophysiology and further experimental and procedural research and tests under global approval.
• Gadolinium agents find use in patients with no renal impairment.

              Active Ingredients

Gadolinium on its own is a natural element but its use in medical science occurs as compound variations called Gadolinium-Based Contrast Agent that are used during the diagnostic tests for CT Scan and MRI. Gadolinium in its +3 ionic oxidation state is a component of GBCAs and used in research and resolution in medicine.

What is it used for?

The basic use of gadolinium in the spectrum of biology and biomedicine is its compound products that work as diagnostic agents during MRI, CT Scan and MRA.

• GBCAs are used are injection products in patients undergoing Magnetic Resonance Imaging and Magnetic Resonance Angiography. This produces a clearer vision of radiology images that make the diagnosis of the patient more accurate.
• GBCAs are also used in Computed Topography Scan commonly known as CT Scan.
• Gadolinium is also used extensively in neutron radiography.

            How does it Work?

Gadolinium as one of the prime research tools in medical science in its compound form is used in ion channel electrophysiology that helps in stretching activated ion channels and blocking sodium leak channels for a clearer vision of the internal diagnostic tests of patients. With electron paramagnetic resonance research moving forward at a speedy rate, gadolinium has found use in measuring the static distance between two amino acid molecules through EPR sensitivity. GBCAs containing gadolinium is used as intravenous injections in patients undergoing the same reactive tests.

            What are the approved uses?

• Gadolinium-Based Contrast Agents are used in the diagnostic tests in permissible amounts during MRIs, CT Scans and MRAs.

• In the medical spectrum, gadolinium may have found use in patients with renal impairments. However, research on the same is still an ongoing process that requires more experimentation and insight.

The permissible dose of Omniscan (linear GBCA) in adults and pediatric patients is 0.2ml/kg as an intravenous injection in the scope for tests along the Central Nervous System.

The permissible dose of Omniscan (linear GBCA) in adults and pediatric patients is 0.1ml/kg as an intravenous injection in the scope for tests for kidney imaging and 0.2ml/kg for intrathoracic, pelvic, intra-abdominal and retroperitoneal region imaging.

          Production Anecdotes/History

U.S Food and Drug Administration or FDA issued a warning against using GBCAs in medical sciences but research work is still going on the determine the safe dosage on people undergoing diagnostic tests that require the use of these agents. The potential risks involving the use of gadolinium in the human body have been outweighed by the current permissible amount of GBCAs that can be used in the human body. 

Another significant point to remember is that different individuals with different biological differentiation can have a varied reaction with GBCAs. Hence, it is imperative for medical practitioners to determine the conditions of each patient and the potential risks before deciding on the dosage. 

Precautions

GBCAs are used in imaging diagnostic studies in MRI for the detection of problems like internal infections, cancerous growths, bleeding and more. However, with its critical use in medicinal research, there are some precautionary points that should be remembered by practitioners:

• Each patient reacts differently to GBCAs and each one of them has their own retention characteristics delivering different risks in patients. People requiring multiple doses of GBCAs, children, pregnant women and ones with a history of inflammation should be carefully studied to see the potential risks of these agents in their systems. 
• Patients with an existing history of critical renal failure or kidney problems should also consider using GBCA. Gadolinium retention often results in a rare condition called Nephrogenic Systemic Fibrosis or NSF, sometimes reaching adverse risks of multiple organ failures. With such a patient under the diagnostic scope, it is important to determine the dosage before any further administration.
• Hypersensitivity reactions due to the use of GBCA Omniscan have been reported to be fatal in some isolated cases. To avoid such complications, patients should be kept under observation for any adverse effect of the same on their health and body.

Long-Term Use Considerations

FDA has issued Gadolinium-Based Contrast Agents under warning scrutiny as people undergoing MRIs can have gadolinium retention in their brain. Although there have not been any identified long-term effect of gadolinium use, people with pre-existing kidney problems may develop an adverse condition called Nephrogenic Systemic Fibrosis or NSF due to long-term exposure to these agents.

Drug Interactions

Till date, there have been no specific drug interactions in the scope of medical sciences.

           Can Interact with the Following

No studies have been concluded on this.

           Can’t Interact with the Following

No studies have been concluded on this.

When to Stop Taking

The administration of GBCAs for prolonged periods of time may result in adverse side effects. However, there is no ongoing prescription for taking gadolinium-based compounds as it is administered only during diagnostic tests involving MRI, MRA and CT Scans.

However, if you already have an existing medical complication or any other substantial condition, it is always better to go for full consultation before any of these can be used.

Long-Term Side Effects

The effects of using GBCA have been found to result in a number of health deteriorations.

• NSF

GBCAs are responsible for increasing the risk of nephrogenic systemic fibrosis or NFS in patients with kidney complications. It has been reported that people with chronic or severe kidney diseases and injuries are most susceptible to developing NFS.

• Hypersensitivity

The use of Omniscan has resulted in anaphylactic and anaphylactoid reactions resulting in death. 

• Acute Renal Failure

Conditions have worsened for patients with pre-existing renal problems just within the first 48 hours of Omniscan(linear GBCA) administration. With increasing does of gadolinium agents, these risks of renal failure may also become adverse. Reports show that only less than 1% patients under the use of Omniscan have suffered renal failure, but the effects cannot be overlooked as a grave potential risk.

FDA Warnings (History Of)

FDA has issued safety warnings for medical practitioners using substantial doses of GBCAs on patients with any medical history. Although the adverse side effects of gadolinium in the biological system do not have any sustainable complications, it is advisable to look for any potential risks when using GBCAs. Examination of the body prior to its use reduces risks by a certain amount curbing any dangerous implications in the future.

Other Common Side Effects

Apart from the adverse effects of GBCAs in the human biological system, there are certain other conditions that have been reported in patients undergoing diagnostic tests with gadolinium agents.

In a clinical study with 1160 patients under the influence of Omniscan, there have been the following moderate reactions among 3% of them:

• Nausea

• Headache

• Dizziness

Adverse reactions in 1% of these patients include:

• Disorders in injection sites

• Vasodilation

• Anaphylactoid reactions including cutaneous, respiratory and cardiovascular symptoms

• Hot flushes

• Fever

• Fatigue

• Rigors

• Pain

• Malaise

• Syncope

• Convulsions including aggravated migraine, tremor, abnormal coordination, sclerosis

• Abdominal pain, dry mouth, diarrhea, vomiting

• Heating disorders like tinnitus

• Abnormality in hepatic functioning

• Musculoskeletal disorders like myalgia and arthralgia

• Respiratory disorders like dyspnea and rhinitis

• Rash

• Excessive sweating

• Loss in taste and taste perversion

• Renal failure

• Abnormality in vision

Lawsuits

People around the world have gone through MRI diagnostic tests for further detection of internal problems. However, research shows that contrast agents that contain gadolinium may run risks of developing adverse side effects. The prescribed quantitative measure of using GBCAs has been identified by the FDA who identifies no dangerous effects of gadolinium-based products in relation with brain retention. However, with the list of side effects that have been produced as evidence and results from extensive research work, there has been an alarming rate of lawsuits against manufacturers and medical practitioners using the agent for internal imaging.

Back in 2007, FDA quoted all gadolinium-based products used in MRIs and MRAs under ‘Black Box Warning’ only for patients who have a history of relatable health issues like disparity in renal functioning and impaired drug elimination issues.

As of 2018, studies and research have shown that the side effects of gadolinium-based contrast agents or GBCAs in patients with normal physiological and renal functioning also reinstate moderate toxicity.

With every medical outcome under scrutiny, communities around the globe are urging FDA to re-evaluate the side effects and whether GBCAs can be used effectively in MRI, MRA and CT Scan in the scope of sustainable diagnosis and internal detection imaging procedural tests.