Acute Porphyria Drug Database

A02BA02 - Ranitidine
Propably not porphyrinogenic
PNP

Rationale
Rantidine is re-classified as PNP. Ranitidine appears to only minimally inhibit hepatic metabolism of some drugs. No observations pointing to clinical CYP induction. The drug maufacturing companies and some national formularies warn against the use of Ranitidine in acute porphyria based on a few case reports. The references indicate that an attack has been associated with Ranitidine, but the clinical data question the causality of this observation. There are uneventfull clinical experiences (n=10), which points to non-porphyrinogenicity.
Chemical description
Aminoalkylfurane. Unlike cimetidine, ranitidine contains an aminoalkyl-substituted furan ring rather than an imidazole ring.
Therapeutic characteristics
Histamine-receptor antagonist used in peptic ulcer and gastro-oesophageal reflux. Oral and intravenous administration.
Hepatic exposure
Significant.
Metabolism and pharmacokinetics
Substrate of CYP1A2, 2C19 and 2D6. Weak CYP 1A2 inhibitor. Inhibitor of augmented CYP-mediated metabolism. Following oral administration, the drug undergoes extensive first-pass metabolism. About 10% of the given dose is excreted as inactive metabolites and the remaining is excreted as unmetabolized ranitidine. The metabolites are N-oxide, S-oxide, and desmethylranitidine; the N-oxide is the major metabolite but accounts for only about 4 to 6% of a dose. About 30% of an oral dose and 70% of an intravenous dose is excreted unchanged in the urine in 24 hours, primarily by active tubular secretion; there is some excretion in the faeces too. Since ranitidine interacts with the hepatic cytochrome P-450 (microsomal) enzyme system differently than does cimetidine, ranitidine appears to only minimally inhibit hepatic metabolism of some drugs (e.g., coumarin anticoagulants, theophylline, diazepam, propranolol). Ranitidine forms a ligand complex with the cytochrome P-450 enzyme system; however, ranitidine appears to interact with different forms of cytochrome P-450 than does cimetidine. The affinity of ranitidine for cytochrome P-450 is about 10% that of cimetidine and the extent of inhibition of the enzyme system is about 2.4 times less than that with cimetidine. Inhibition of hepatic microsomal enzyme activity appears to be structurally determined rather than associated with H2-receptor blockade, since ranitidine and cimetidine differ substantially in their effects on this enzyme system.
Personal communication
Used in Swedish Porphyria wards. Patient reports : tolerated (n=2). Used by 1 AIP patient with unknown susceptibility , Norway.
IPNet drug reports
Uneventful use reported in 24 patients with acute porphyria.

References

  1. Scientific articles
  2. Carmen Martínez et al.Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists.PMID: 10223772. PMID 10223772. #4328
  3. Rendic S, Drug Metabolism Reviews 2002, Summary of information on human cyp enzymes Human P40 metabolism data.pdf. #3259
  4. Bhadoria DP et al. Ranitidine and acute intermittent porphyria. J Assoc Physicians India. 1988 Apr;36(4):295-6. PMID: 3182690. PMID 3182690. #4326
  5. Brouard A et al. H2-receptor antagonists and acute intermittent porphyria. Am J Hosp Pharm. 1991 Jun;48(6):1190-1. PMID: 1858794. PMID 1858794. #4325
  6. Pratap D et al. Can ranitidine induce porphyria. J Assoc Physicians India. 1988 Mar;36(3):237-8. PMID: 3182677. PMID 3182677. #4327
  7. Tripathi SK. Ranitidine and porphyria--causal or coincidental? J Assoc Physicians India. 1988 Nov;36(11):680.PMID: 3249005. PMID 3249005. #3384
  8. Drug reference publications
  9. AHFS #3257
  10. Martindale #3258

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