Clinical benefit from PANHEMATIN depends on prompt
administration. Attacks of porphyria may progress to a point where irreversible
neuronal damage has occurred. PANHEMATIN therapy is intended to prevent an
attack from reaching the critical stage of neuronal degeneration. PANHEMATIN is
not effective in repairing neuronal damage.9
Recommended dosage guidelines should be strictly
followed. Reversible renal shutdown has been observed in a case where an
excessive hematin dose (12.2 mg/kg) was administered in a single infusion.
Oliguria and increased nitrogen retention occurred although the patient
remained asymptomatic.4 No worsening of renal function has been seen
with administration of recommended dosages of hematin.9
A large arm vein or a central venous catheter should be
utilized for the administration of PANHEMATIN to avoid the possibility of
Since reconstituted PANHEMATIN is not transparent, any
undissolved particulate matter is difficult to see when inspected visually.
Therefore, terminal filtration through a sterile 0.45 micron or smaller filter
Because increased levels of iron and serum ferritin have
been reported in postmarketing experience, physicians should monitor iron and
serum ferritin in patients receiving multiple administrations of PANHEMATIN
(See “ADVERSE REACTIONS” section).
Tests for Diagnosis and Monitoring of Therapy
Before PANHEMATIN therapy is begun, the presence of acute
porphyria must be diagnosed using the following criteria:9
- Presence of clinical symptoms.
- Positive Watson-Schwartz or Hoesch test. (A negative
Watson-Schwartz or Hoesch test indicates a porphyric attack is highly unlikely.
When in doubt quantitative measures of δ-aminolevulinic acid and
porphobilinogen in serum or urine may aid in diagnosis.)
Urinary concentrations of the following compounds may be monitored
during PANHEMATIN therapy. Drug effect will be demonstrated by a decrease in
one or more of the following compounds.3-6
ALA – δ-aminolevulinic acid
UPG – uroporphyrinogen
PBG – porphobilinogen coproporphyrin
Carcinogenesis, Mutagenesis, Impairment of Fertility
PANHEMATIN was not mutagenic in bacteria systems in vitro
and was not clastogenic in mammalian systems in vitro and in vivo. No data are
available on potential for carcinogenicity or impairment of fertility in
animals or humans.
Teratogenic effects - Pregnancy Category C
Animal reproduction studies have not been conducted with
hematin. It is also not known whether hematin can cause fetal harm when
administered to a pregnant woman or can affect reproduction capacity. For this
reason PANHEMATIN should not be given to a pregnant woman unless the expected
benefits are sufficiently important to the health and welfare of the patient to
outweigh the unknown hazard to the fetus.
It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk, caution should be
exercised when PANHEMATIN is administered to a nursing woman.
Safety and effectiveness in pediatric patients under 16
years of age have not been established.
Clinical studies in PANHEMATIN did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical experience has not
identified differences in response between the elderly and younger patients. In
general, dose selection for an elderly patient should be cautious, usually
starting at the low end of the dosing range, reflecting the greater frequency
of decreased hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy.
3. Lamon, J. M., Hematin Therapy for Acute Porphyria,
Medicine 58(3):252-269, 1979.
4. Dhar, G J., et al., Effects of Hematin in Hepatic
Porphyria, Ann Intern Med 83:20-30, 1975.
5. Watson, C. J., et al., Use of Hematin in the Acute
Attack of the “Inducible” Hepatic Porphyrias, Adv Intern Med 23:265-286, 1978.
6. McColl, K. E., et al., Treatment with Haematin in
Acute Hepatic Porphyria, Q J Med, New Series L (198):161-174, Spring, 1981.
9. Pierach, C. A., Hematin Therapy for the Porphyric
Attack, Semin Liver Dis 2(2):125-131, May, 1982.