How Argatroban works
Argatroban interferes with blood clotting by inhibiting the enzyme involved, thrombin – the active ingredient is therefore a direct thrombin inhibitor.
Thrombin is normally activated by enzymes that have themselves been activated by vascular damage or foreign bodies in the bloodstream. It then converts fibrinogen at the affected site to fibrin – the “glue” that holds the resulting blood clot together.
By inhibiting thrombin, Argatroban interferes with this process. However, it is only used in patients who have previously had what is known as heparin-induced thrombocytopenia (HIT) type II. This is a form of platelet deficiency that can be triggered as a dangerous side effect of treatment with the anticoagulant heparin.
Blood clotting is not inhibited in those affected, but paradoxically increased. These patients must therefore not receive any more heparin under any circumstances, as otherwise numerous blood clots can form in the bloodstream and clog the vessels. Instead, Argatroban is used to maintain anticoagulation.
Absorption, degradation and excretion
When is Argatroban used?
Argatroban is used in adult patients with heparin-induced thrombocytopenia (HIT) when they require anticoagulant therapy.
The duration of treatment should not exceed two weeks. In individual cases, therapy may be given for a longer period under medical supervision.
How Argatroban is used
The anticoagulant Argatroban is only commercially available as a concentrate for the preparation of an infusion solution. This concentrate is diluted by the physician and then administered by infusion or syringe pump. The amount of active ingredient administered depends on the patient’s weight and state of health.
During treatment, the coagulation values must be monitored closely.
What are the side effects of Argatroban?
One in ten to one hundred people treated with Argatroban experience side effects in the form of anemia, bleeding, blood clots in the deep veins, nausea and purpura (many pinhead-sized hemorrhages under the skin).
In addition, side effects occasionally develop, including infections, loss of appetite, low sodium and blood sugar levels, headache, dizziness, impaired vision and speech, numbness, high or low blood pressure, palpitations and other heart problems.
What should be considered when using Argatroban?
Contraindications
Argatroban must not be used in:
- hypersensitivity to the active substance or to any of the other components of the drug
- uncontrolled bleeding
- severe hepatic impairment
Drug interactions
If Argatroban is given concomitantly with other anticoagulants (such as ASA/acetylsalicylic acid, clopidogrel, phenprocoumon, warfarin, dabigatran), the risk of bleeding may be increased. This also applies to the use of ASA as an analgesic, ibuprofen and diclofenac (other analgesics).
The infusion preparations containing the active ingredient argatroban contain ethanol (potable alcohol) to improve solubility. They thus pose a possible health risk for liver patients, alcoholics, epileptics and patients with certain brain diseases. Also, interactions with metronidazole (antibiotic) and disulfiram (drug for alcohol dependence) cannot be ruled out.
Age restriction
Data on the use of Argatroban in children and adolescents under 18 years of age are limited. No recommendations can be made regarding dosage.
Pregnancy and lactation
It is not known whether argatroban passes into breast milk. Animal studies in rodents with radiolabeled argatroban showed accumulation in breast milk. For safety reasons, use in nursing mothers is therefore not recommended. If necessary, breastfeeding must be interrupted for the duration of treatment.
How to obtain medicines containing Argatroban
Argatroban is available only on prescription in Germany, Austria and Switzerland, but is not prescribed on prescription because it must be used in an inpatient setting under a doctor’s supervision.
How long has Argatroban been known?
The anticoagulant Argatroban was first approved in Japan in 1990. Ten years later, the drug received approval in the United States for the treatment of blood clots in patients with HIT.
In 2002, approval was extended to patients who had previously had HIT or were at risk for it. The first product available in Germany and Austria with the active ingredient argatroban was approved in 2010. Approval in Switzerland followed in 2014.
