Embryotoxic drugs

Mebendazole is contraindicated in patients witii known hypersensitivity. Mebendazole is also contraindicated during pregnancy (Category C). The drug, like albendazole, has exhibited embryotoxic and teratogenic effects in experimental animals. Administration of mebendazole with tiie hydantoins and carbamazepine may reduce plasma levels of mebendazole. 

Korhonen A, Hemminki K, Vainio H. 1983a. Embryotoxic effects of phthalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos. Drug Chem Toxicol 6 191-207. 

Anterior uveitis and neutropenia are fairly common side effects of cidofovir therapy. Ocular hypotony and metabolic acidosis are rare. Exposure to therapeutic levels of cidofovir causes cancer in rats therefore, this drug should be considered a potential human carcinogen. Animal studies have also shown cidofovir to produce embryotoxic and teratogenic effects and to impair fertility. 

Korhonen, A., Hemminki, K. Vainio, H. (1983a) Toxicity of rubber chemicals towards three-day chicken embryos. Scand. J. Work Environ. Health, 9, 115-119 Korhonen, A., Hemminki, K. Vainio, H. (1983b) Embryotoxic effects of phtalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos. Drug chem. Toxicol, 6, 191-207... 

This is a sedative drug with low adult toxicity, which proved to be a very potent human teratogen, causing phocomelia (shortening of the limbs) and other defects when taken between the third and eighth week. In some cases, only a few doses were taken, but on the critical days (e.g., days 24-27 for phocomelia of arms). It is not readily reproducible in laboratory animals (e.g., rats). Mechanism is unknown, but a metabolite suspected, possibly produced by cytochrome P-450. A number of metabolites are produced and some chemical breakdown occurs. Phthalylglutamic acid metabolite is teratogenic in mice. Thalidomide may acylate nucleic acids and polyamines. The S-enantiomer is more embryotoxic than the R-enantiomer. 

The primary adverse effect of intravenous cidofovir is a dose-dependent nephrotoxicity. Concurrent administration of other potentially nephrotoxic agents (eg, amphotericin B, aminoglycosides, nonsteroidal anti-inflammatory drugs, pentamidine, foscarnet) should be avoided. Prior administration of foscarnet may increase the risk of nephrotoxicity. Other potential side effects include uveitis, decreased intraocular pressure, and probenecid-related hypersensitivity reactions. Neutropenia and metabolic acidosis are rare. The drug caused mammary adenocarcinomas in rats and is embryotoxic. 

Efavirenz NNRTI 600 mg qd Not to be taken with a fatty meal Dizziness, insomnia, rash, transaminitis Embryotoxic see footnote 2 for concurrent drug contraindication s... 

ToxScope Function Based Drug Design, V.N. Orekhovich Institute of Biochemical Chemistry LeadScope Inc. www.leadscope.com/products/txs.htm teratogenicity, embryotoxicity, and many other effects Carcinogenicity and many... 

Adverse effects Amantadine s side effects are mainly associated with the CNS. Minor neurologic symptoms include insomnia, dizziness, and ataxia. More serious side effects have been reported (for example, hallucinations, seizures). The drug should be employed cautiously in patients with psychiatric problems, cerebral atherosclerosis, renal impairment, or epilepsy. Rimantadine causes fewer CNS reactions since it does not efficiently cross the blood-brain barrier. Amantadine and rimantadine should be used with caution in pregnant and nursing mothers, because they have been found to be embryotoxic and teratogenic in rats. 

Pegylated liposomal doxorubicin is embryotoxic in rats and embryotoxic and abortifacient in rabbits. Teratogenicity cannot therefore be ruled out, but there is no reported experience in pregnant women. Equally, it is not known if the drug is excreted into human breast milk, so breastfeeding should be discontinued before the administration of pegylated liposomal doxorubicin. 

Deferiprone inhibits intracellular ribonucleotide reductase, a rate-limiting enzyme in DNA sjmthesis, and in animal experiments it is toxic to prohferating tissues, especially the bone marrow. It has a pattern of adverse effects similar to those of cytotoxic drugs and is teratogenic and embryotoxic in animals (14,37). 

There is evidence that vinca alkaloids are teratogenic. Vinblastine caused malformations after first trimester administration (88-90). However, since vinca alkaloids are often combined with other cytotoxic drugs, it is difficult to relate any teratogenic effect to the vinca alkaloid alone (88). In mice and rabbits, vinblastine was embryotoxic and fetotoxic (89). However, it is unclear whether vinca alkaloids can cross the placenta because of their high molecular weights (about 1000 g/mol). 

The drug thalidomide serves to illustrate the first of these points with respect to hypnotic potency, the (S)-(—), (ii)-(+) and (i S)-( ) racemate of thalidomide are all equally active, as tested by prolonging of sleep induced by phenobarbitol. (5)-(-)-Thalidomide, but not (/f)-(+)-thali-domide, is transformed in vivo to L-A -phthaloylglutamine and L-Af-phthaloylglutamic acid, products that are both embryotoxic and teratogenic in SWS mice and Natal rats. The d isomers of these products, formed by the drug, are not. ... 

Huxtable RJ. Human embryotoxicity of pyrrolizidine-containing drugs. Hepatology 1989 9 510-1. 

However, just as with other toxic effects, either the parent drug or a metabolite may be responsible for embryotoxicity, but it is often difficult to predict which, without substantial metabolic and biochemical data being available. 

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