Source: Health Products Regulatory Authority (IE) Revision Year: 2016 Publisher: NordMedica A/S, Jaegersborg, Alle 164, DK-2820, Gentofte, Denmark
Amsacrine should only be used under strict control of a specialised oncologist, with preference in institutions with experience with this kind of therapies.
Amsacrine can cause severe bone-marrow-depression, thus frequent blood control is necessary. Infections and hemorrhages can be fatal. With an already existing bone-marrow-depression caused by drugs, amsacrine should be administered cautiously and with extra controls. Also if a too strong decrease in white blood cells or blood platelets occurs, interruption of the amsacrine treatment or decrease of dosage can be necessary. Red blood cells and platelets should be available for transfusion as well as other facilities for the treatment of bone-marrow-depression.
Amsacrine can induce hyperuricemia secondary to rapid lysis of neoplastic cells. Careful monitoring of blood uric acid levels is recommended, in particular with regard to possible consequences for renal function. Consideration may be given to reducing uric acid levels prophylactically, prior to or concurrent with amsacrine treatment.
Toxicity at recommended doses is enhanced by hepatic or renal impairment. Laboratory evaluation of hepatic and renal function is necessary prior to and during administration. A dose reduction might be considered.
The physician should be aware of allergic reactions (anaphylaxia, oedema and skin reactions), GI problems and epileptic insults (epileptic seizures related to the use of amsacrine, can be treated according to standard regimen.
Local necrosis can occur with extravasation of amsacrine (see section 4.8). Injection site irritation can be prevented by diluting amsacrine in a greater volume 5% glucose and infusion is spread over a larger period of time (minimal 1 hour).
Careful monitoring of cardiac rhythm is recommended for detection of cardiotoxicity. Patients with hypokalemia are at increased risk of ventricular fibrillation. The risk of developing arrhythmias can be minimized by ensuring a normal serum potassium level immediately prior to and during amsacrine administration. Hypokalemia should be corrected prior to amsacrine administration.
Complete blood counts, liver and renal function tests, and electrolytes should be performed regularly. Electrolytes should be re-evaluated before each day’s treatment
Concomitant influenza or pneumococcal vaccination and immunosuppressive therapy have been associated with impaired immune response to the vaccine.
Amsacrine may be displaced from serum albumin, with consequential increase in free drug and toxicity if used with other highly protein binding drugs.
Adverse effects may be potentiated by use with other cytotoxic agents.
Data on the usage of this compound during pregnancy in patients are not available to judge possible harmfulness. However based on its pharmacologic activity harmfulness of treatment during pregnancy is possible.
In animal studies teratogenicity and other reproductivity toxicity has been observed (see section 5.3). Based on animal studies and the mechanism of action of the substance, use during pregnancy is discouraged, especially during the first trimester.
In every individual case the advantages of treatment should be weighed against the risks to the foetus.
Due to the mechanism of action of amsacrine and possible adverse effects on the foetus, females should use effective contraception for 3 months after treatments and males for 6 months after treatment.
Reversible azospermia in humans has been described.
As it is not clear whether amsacrine is excreted in the mother milk, lactation is contraindicated.
No data about this influence are known. In view of reported adverse effects profile patients are advised after administration of amsacrine to be cautious when driving or using machines.
The most common adverse reactions are nausea and/or vomiting, anemia, fever and infection. Pain or phlebitis on infusion has been reported.
All patients treated with a therapeutic dosage of amsacrine show bone marrow depression. Main complications are infections and hemorrhages. Minimal white blood cells occur on day 5-12, usually followed with complete recovery on day 25. The pattern of inhibition of blood platelets is similar to that of leucocytes.
In the table below all adverse events are presented according to classification of organ system and frequency, very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10.000 to <1/1000); not known (cannot be estimated from the available data).
Common: Infection
Common: Thrombocytopenia, pancytopenia, hemorrhage
Rare: Anemia, granulocytopenia, leukopenia
Rare: Hypersensitivity, anaphylactic reaction, oedema
Common: Hypokalemia
Rare: weight decreased, weight increased
Not known: Hyperuricaemia
Common: Affect lability
Rare: Lethargy, confusion
Common: Grand mal seizure1
Rare: Headache, hypoesthesia, dizziness, periferal neuropathy
Rare: Visual disturbances
Common: Cardiotoxicity, arrhythmia, congestive heart failure2
Rare: Atrial fibrillation, sinus tachycardia, ventricular fibrillation3, ventricular arrhythmias, cardiomyopathy, bradycardia, ECG abnormal, ejection fraction decreased
1 Sometimes paired with hypokalemia
2 especially in paediatric patients, pretreated with antracyclines
3 fatal or lifethreathening, usually in patients with hypokalemia
4 Mucosa of mouth and tractus digestivus are frequently effected ranging in severity from mild to life-threatening. Total oral mucosa can be affected; recovery takes several weeks.
5 related to the concentration of amsacrine infused (see section 4.4)
Amsidine is incompatible with saline. Amsidine in solution reacts with plastic syringes.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
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