Holoxan Dosage/Direction for Use

Holoxan should only be administered by an experienced oncologist. The dosage must be adapted to each patient individually. In single-drug therapy of adults, the most common treatment is based on fractionated doses. In the absence of individual prescriptions, the following recommendations may serve as a guideline.
In general, Holoxan is given IV in divided doses of 1.2-2.4 g/m² body surface (up to 60 mg/kg body weight) daily for 5 consecutive days (the duration of these infusions is about 30-120 min, depending on the volume). Holoxan may also be given in a single high dose, usually as a 24-hr prolonged infusion. The dosage is generally 5 g/m² body surface (125 mg/kg body weight) and should not exceed >8 g/m² body surface (200 mg/kg body weight)/cycle. A single high dose may cause higher hemato-, uro-, nephro- and CNS toxicity.
Care should be taken to ensure that the ifosfamide concentration of the solution does not exceed 4%.
In combination therapy with other cytostatics, the dose should be adapted to the type of therapeutic scheme.
Because of its urotoxicity, ifosfamide should, as a matter of principle, be used in combination with mesna. Other toxicities and the therapeutic effects of ifosfamide will not be influenced by mesna. Should cystitis with micro- and macrohematuria develop during therapy, the treatment should be discontinued until the patient has recovered.
Because the cytostatic effect of ifosfamide occurs only after activation in the liver, there is no danger of injuring the tissue in the case of paravenous injections.
The therapy cycles may be repeated every 3-4 weeks. The intervals will depend on the blood count and on the recovery from any adverse reactions or side effects.
The administration of uroprotection with uroprotector, Uromitexan (mesna) as directed, should be maintained.
Regular blood counts, regular checks of renal function and regular urinalysis including urinary sediment are necessary.
Timely administration of antiemetics is indicated, and the additional influences on the CNS in connection with Holoxan should be taken into consideration.
Preparation of the Solution: The handling of Holoxan should always be in accordance with the safety precautions used for handling of cytotoxic agents.
To prepare a 4% isotonic solution ready for injection, water for injection is added to the dry substance in the following amounts: Water for injection 13, 25 and 50 mL for Holoxan 500 mg, 1 g and 2 g, respectively.
The substance dissolves readily if the vials are vigorously shaken for 0.5-1 min after the addition of water for injection. If the substance fails to dissolve immediately and completely, it is advisable to allow the solution to stand for a few minutes. The prepared solution can be kept for up to approximately 24 hrs if stored at a temperature not exceeding +8°C (refrigerator). The Holoxan solution for short-term IV infusion (approximately 30-120 min) is prepared by diluting the aforementioned solution with 250 mL Ringer's solution or 5% glucose solution or physiological saline. For longer infusions over 1-2 hrs, dilution is recommended with 500 mL Ringer's solution or 5% glucose solution or physiological saline. For continuous 24-hr infusions of high-dose Holoxan, the prepared Holoxan solution eg, 5 g/m², must be diluted to 3 L with 5% glucose solution and/or physiological saline.
Note: Because of its alkylating action, ifosfamide is a mutagenic and also a potential carcinogenic substance. Contact with the skin and mucous membranes should therefore be avoided.