Thrombonorm Capsules are indicated for the treatment of patients with:
• Secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events.
Dosage and Administration
- For adult patients is 0. 5 mg q.i.d or 1 mg b.i.d which should be maintained for at least one week.
- Starting dose for pediatric patients have ranged from 0.5 mg per day to 0.5 mg q.i.d as there is limited data on
the appropriate starting dose for pediatric patients an initial dose of 0.5 mg per day is recommended.
- In both Adult & Pediatric Patients Dosage should then be adjusted to the lowest effective dosage required to reduce
and maintain platelet count below 600,000/uL, and ideally to the normal range.
- The dosage should be increased by not more than 0.5 mg/day in any one week. Maintenance dosing is not expected to be different between adult &pediatric patients.
- Dosage should not exceed 10 mg/day or 2.5 mg in a single dose.
- There are no special requirements for dosing the geriatric population.
- It is recommended that patients with moderate hepatic impairment start anagrelide therapy at a dose of 0.5 mg/day and be maintained for a minimum of one week with careful monitoring of cardiovascular effects.
- The dosage increment must not exceed more than 0.5 mg/day in any one-week.
- The potential risks and benefits of anagrelide therapy in a patient with mild and moderate impairment of hepatic function should be assessed before treatment is commenced.
- Use of anagrelide in patients with severe hepatic impairment has not been studied thus the use of anagrelide in patients with severe hepatic impairment is contraindicated.
- To monitor the effect of anagrelide and prevent the occurrence of thrombocytopenia, platelet counts should be performed every two days during the first week of treatment and at least weekly thereafter until the maintenance dosage is reached.
- Typically, platelet count begins to respond within 7 to 14 days at the proper dosage. The time to complete response, defined as platelet count ² 600,000/uL, ranged from 4 to 12 weeks.
- Most patients will experience an adequate response at a dose of 1.5 to 3.0 mg/day.
- Patients with known or suspected heart disease, renal insufficiency, or hepatic dysfunction should be monitored closely.
- Anagrelide is contraindicated in patients with severe hepatic impairment.
- Exposure to anagrelide is increased 8-fold in patients with moderate hepatic impairment. Use of anagrelide in patients with severe hepatic impairment has not been studied.
The most frequently reported adverse reactions to anagrelide (in 5% or greater of 942 patients with myeloproliferative disease)
in clinical trials were:
• Headache, Dizziness.
• Diarrhea, Nausea, Vomiting, Abdominal pain, Flatulence.
• Edema, Peripheral Edema.
• Pain, Back pain, Dyspnea, Fever.
• Rash including urticarial.
• Chest Pain, Anorexia, Tachycardia, Palpitations.
• Pharyngitis, Malaise, Cough.
• Paresthesia, Pruritus & Dyspepsia.
- An in vivo interaction study in humans demonstrated that a single 1mg dose of anagrelide administered concomitantly with
a single 900 mg dose of aspirin was generally well tolerated.
- There was no effect on bleeding time, PT or a PTT.
- No clinically relevant pharmacokinetic interactions between anagrelide and acetylsalicylic acid were observed.
- In that same study, aspirin alone produced a marked inhibition in platelet aggregation ex vivo.
- Anagrelide alone had no effect on platelet aggregation, but did slightly enhance the inhibition of platelet aggregation by aspirin.
- Anagrelide is metabolized at least in part by CYP1A2.
It is known that CYP1A2 is inhibited by several medicinal products, including fluvoxamine, and such medicinal products could theoretically adversely influence the clearance of anagrelide.
Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other coadministered medicinal products sharing that clearance mechanism e.g. theophylline.
- Anagrelide is an inhibitor of cyclic AMP PDE III.
- The effects of medicinal products with similar properties such as inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide.
Pregnancy and Lactation
• There are no adequate and well-controlled studies in pregnant women.
• Anagrelide hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Anagrelide is not recommended in women who are or may become pregnant.
• If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
• Women of child-bearing potential should be instructed that they must not be pregnant and that they should use contraception while taking anagrelide.
• Anagrelide may cause fetal harm when administered to a pregnant woman.
• It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reaction in nursing infants from anagrelide hydrochloride, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Warning and Precaution
Anagrelide therapy requires close clinical supervision of the patient.
• While the platelet count is being lowered (usually during the first two weeks of treatment).
• Blood counts (hemoglobin, white blood cells).
• Liver function (SGOT, SGPT).
• Renal function (serum creatinine, BUN) should be monitored.
In 9 subjects receiving a single 5 mg dose of anagrelide, standing blood pressure fell an average of 22/15 mm Hg, usually accompanied by dizziness. Only minimal changes in blood pressure were observed following a dose of 2 mg.
Cessation of Thrombonorm Treatment:
In general, interruption of anagrelide treatment is followed by an increase in platelet count. After sudden stoppage of anagrelide therapy, the increase in platelet count can be observed within four days.
Package and Storage
- Package: Carton box contains 10 strips each strip contains 10 Capsules.
- Storage: Don't store above 25 °C