Read the page Obtaining haem arginate for information about availability.

Principles

Effect of haem arginate to reduce porphyrin synthesis

Haem arginate consists of haem complexed with the amino acid arginine. This forms a stable compound. Haem arginate works by replenishing haem stores within the body. By negative feedback, this inhibits the initial rate-limiting enzyme of the haem synthetic pathway, ALA synthase, as shown here (Click on the image for a detailed diagram). The formation of porphyrins and the precursors ALA and PBG is almost immediately reduced to low levels, and the symptoms improve. Haem arginate is safe. The most frequent complication is phlebitis at the site of infusion. This can be reduced by giving the infusion of haem arginate in a protein buffer such as stabilised human serum or human serum albumin.

Indications for Haem Arginate

Any severe attack

Any attack complicated by severe symptoms, hyponatraemia, convulsions, indicators of incipient neuropathy (including loss of reflexes or complaints of pain in the muscles of the back, thighs and upper arms).

An acute attack which does not improve within 24 hours of admission

Experience suggests that if a clear spontaneous improvement is not evident within 24 hours, the hospital stay is likely to be prolonged; early administration of haem arginate will significantly shorten the period of illness and hospitalisation and should therefore be given.

Patients who suffer frequent, repeated acute attacks

There are a few patients, (almost exclusively with acute intermittent porphyria), who suffer recurrent attacks. In many of these, prior experience will have shown that attacks do not settle unless haem arginate is given (See Dealing with recurrent acute attacks of porphyria).

Recurrent attacks in patients recovering from, or with residual neuropathy

Recurrent attacks may lead to further decline in nerve function or to loss of function already recovered in patients who show evidence of neuropathy as a result of previous attacks. Haem arginate therapy should therefore not be delayed in these patients.

Cost-Effectiveness

Haem arginate is expensive. The price of four ampoules currently approaches 20,000 rand. The expense can be minimised by the following:

  • By withholding its use except where the indications described above exist. Approximately 40% of all acute attacks, particularly those in patients with variegate porphyria, will remit spontaneously with conservative therapy. In apparently mild attacks therefore it is reasonable to observe the patient for the first 24 hours before going ahead with the use of haem arginate.
  • By using a standard dose of 5 ml (250 mg) per dose, rather than the mg/kg dose indicated in the package insert. This standard dose is, in our experience, effective. Each ampoule as supplied contains 10 ml; this allows the use of two ampoules per attack and halves the expense.

Used for the correct indications, haem arginate is highly cost-effective, and this point must be driven home to hospital and medical scheme administrators. The cost of a course of therapy should be contrasted with the cost of a 6-month hospitalisation for quadriparesis, 3 months of which may be spent on a ventilator in an intensive care unit, and a lengthy period of rehabilitation.

Availability

Read the page Obtaining haem arginate for information about availability.

Note that there is usually a delay in obtaining the haem arginate from the supplier, and it is difficult to arrange for delivery of hours and over weekends. It is therefore important to start arrangements for the delivery of haem arginate as soon as you foresee that its use may be necessary.

For international availability, visit the European Porphyria Initiative for details.

Use a standard dose of 250 mg (5 ml) given daily for four days. Mix the haem arginate into 100 ml human serum albumin or stabilised human serum. Infuse intravenously over 20 minutes.

Effect of Therapy

Urine ALA, PBG and porphyrins will be dramatically reduced within 24 hours. Symptoms begin improving after 24 hours, are usually much improved by 48 hours, and patients are ready for discharge by the third or fourth day. Note that haem arginate will not reverse established neuropathy. It is therefore essential to commence therapy before neuropathy develops. Haem arginate unfortunately cannot be used prophylactically, indeed too frequent use may, by inducing the enzyme haem oxygenase, induce its own catabolism with resultant loss of effect. Read Dealing with recurrent acute attacks of porphyria.