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Philosophy of AR > Animal Testing Index > Anti-vivisection Index

Vernon Coleman
Fifty Drugs That Prove Animal Experiments Are Worthless

The following extract is taken from Vernon Coleman's book 'Betrayal of Trust' (published by the European Medical Journal).

The information which follows was taken from the individual data sheets produced by the relevant drug companies. I have included this huge number of drugs because it is the very quantity of drugs on the market - despite the fact that these products are known to cause serious or potentially serious problems in animals - which is of significance (though I do stress that this list is by no means comprehensive). Many of these drugs are extremely popular and are prescribed for millions of patients around the world. It is impossible to obtain precise figures for the number of patients involved because of the secrecy laws.

It would seem to me logical to argue that if animal experiments are worth doing then, (unless the benefit of using a drug can be shown clearly to outweigh the potential hazard), all these drugs should be taken off the market immediately - whereas if these drugs are considered safe for human patients then there is no point in continuing with animal experiments.

These short sections are intended only to illustrate the point I want to make and are not intended to provide useful information about the drugs concerned.

 


 

ABBOTT LABORATORIES LTD
HYTRIN
Containing terazosin as terazosin hydrochloride.

Use: Hytrin is indicated in the treatment of mild to moderate hypertension.
Contra-indications, warnings etc - Carcinogenicity: Hytrin has been shown to produce tumours in male rats when administered at a high dose over a long period of time. No such occurrences were seem in a similar study in mice. The relevance of these findings with respect to the clinical use of the drug in man is unknown.

 



ASTRA PHARMACEUTICALS LTD
LOSEC
Contains omeprazole as enteric-coated granules.

Use: Treatment of reflux oesophagitis. Treatment of duodenal and benign gastric ulcers including those complicating NSAID therapy.
Contra-indications, warnings, etc - Animal toxicology: Gastric ECL-cell hyperplasia and carcinoids, localised to the oxyntic mucosa, have been observed in life-long studies in rats. These changes have been related to sustained hypergastrinaemia secondary to acid inhibition, and not from a direct effect of any individual drug. No treatment related mucosal changes have been observed in patients treated continuously for periods up to 5 years.

 



BAYER plc
DTIC-DOME
Active ingredient: 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide prepared as the citrate salt (dacarbazine).

Use: metastatic malignant melanoma, sarcoma, Hodgkin's disease.
Contra-indications, warnings, etc - Studies have demonstrated this agent to have a carcinogenic and teratogenic effect when used on animals.

 



BENCARD
RIDAURA TILTAB TABLETS
Containing 3 mg auranofin.

Use: In the management of adults with active progressive rheumatoid arthritis only when non-steroidal anti-inflammatory drugs have been found to be inadequate alone to control the disease, i.e. when second-line therapy is required.
Contra-indications, warnings, etc - Gold has been shown to be carcinogenic in rodents although there was no evidence of carcinogenicity in 7 year dog studies.

 



BOEHRINGER MANNHEIM UK (PHARMACEUTICALS) LTD
BEZALIP
Contains bezafibrate.

Use: In hyperlipidaemias of Type 11a, 11b, 111, 1V and V.
Contra-indications, warnings, etc - Warnings: The chronic administration of a high dose of bezafibrate to rats was associated with hepatic tumour formation in females. This dosage was in the order of 30 to 40 times the human dosage. No such effect was apparent at reduced intake levels approximating more closely to the lipid-lowering dosage in humans.
(Author's note: Drug companies often excuse animal results by claiming that the dosage used in animal tests was far higher than that used in human beings. If such studies are irrelevant because of the high dosage then why do them?)

 



BOEHRINGER MANNHEIM UK
SPIROCTAN
Contains spironolactone

Use: Spiroctan is recommended for the treatment of congestive cardiac failure, cirrhosis with ascites and oedema, malignant ascites, nephrotic syndrome and also for diagnosis and treatment of primary hyperaldosteronism.
Contra-indications, warnings, etc - Carcinogenicity:Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not certain.

 



BRISTOL-MYERS PHARMACEUTICALS
BiCNU
Contains a 30 ml vial containing 100 mg carmustine and a 5 ml vial containing 3 ml sterile ethanol diluent.

Use: BiCNU is indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:

1. Brain tumours - Glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumours.
2. Multiple myeloma - in combination with prednisone.
3. Hodgkin's Disease - As secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.
4. Non-Hodgkin's lymphomas - As secondary therapy as above.

Contra-indications, warnings, etc - BiCNU is carcinogenic in rats and mice, producing a marked increase in tumour incidence in doses approximating those employed clinically.

 



CIBA LABORATORIES
APRESOLINE
Contains Hydralazine Hydrochloride.

Use: Hypertension
Contra-indications, warnings etc - Warnings: Hydralazine, in lifetime carcinogenicity studies, caused, towards the end of the experiments, small but statistically significant increases in lung tumours in mice and in hepatic and testicular tumours in rats. These tumours also occur spontaneously with fairly high frequency in aged rodents. With due consideration of these animal and in-vitro toxicological findings, hydralazine in therapeutic doses does not appear to bear a risk that would necessitate a limitation of its administration. Many years of clinical experience have not suggested that human cancer is associated with hydralazine use.

 



CILAG LTD
TOLECTIN 200/400 MG CAPSULES
Contains tolmetin sodium dihydrate.

Use: Rheumatoid arthritis,; osteoarthritis; ankylosing spondylitis; peri-articular disorders such as fibrositis and bursitis.
Contra-indications, warnings, etc - Renal papillary necrosis has occurred in animals after long term administration although there has been no evidence of renal toxicity in clinical trials.

 



CP PHARMACEUTICALS LTD
CHENDOL 125 and CHENDOL 250
Contains chenodeoxycholic acid.

Use: For dissolution of radiolucent cholesterol-rich gallstones in functioning gall bladders. It has a particular place where surgery is contra-indicated or those patients anxious to avoid surgery.
Contra-indications, warnings, etc Precautions: Chenodeoxycholic acid, given in long term studies at doses of 600 mg/kg/day to rats and 1000 mg/kg/day to mice, induced malignant liver cell tumours in female rats and male mice. The clinical significance of these findings is not known.

 



EVANS MEDICAL LTD
NORMAX
Contains danthron docusate sodium.

Use: Constipation in geriatric practice. Analgesic-induced constipation in terminally ill patients of all ages. Constipation in cardiac failure and coronary thrombosis ( conditions in which defaecation must be free of strain).
Contra-indications, warnings, etc - Precautions: In experimental animals, danthron has been associated with adenocarcinomas in the bowel and tumours in the liver.

 



FARMITALIA CARLO ERBA LTD
FARLUTAL
Contains medroxyprogesterone acetate.

Use: Palliative treatment of hormone-sensitive malignancies. Farlutal has been successfully used to produce regressions in breast, endometrial, prostatic and renal cell carcinoma.
Contra-indications, warnings, etc Precautions: It should be noted that long term administration of medroxyprogesterone acetate to beagle dogs has resulted in the development of mammary nodules which were occasionally found to be malignant. The relevance of these findings to humans has, however, not been established.

 



FARMITALIA CARLO ERBA LTD
PHARMORUBICIN RAPID DISSOLUTION
Contains epirubicin hydrochloride with lactose and hydroxybenzoate.

Use: Antimitotic and cytotoxic.
Contra-indications, warnings, etc Like most other anticancer agents, epirubicin has shown mutagenic and carcinogenic properties in animals.

 



FARMITALIA CARLO ERBA LTD
ZAVEDOS
Contains idarubicin hydrochloride with lactose.

Use: Antimitotic and cytotoxic agent.
Contra-indications, warnings, etc Warnings: Like most other cytotoxic agents, idarubicin has mutagenic properties and it is carcinogenic in rats.

 



GEIGY PHARMACEUTICALS TEGRETOL
Active ingredient: Carbamazepine.

Use: Epilepsy generalised tonic-clonic and partial seizures.
Contra-indications, warnings, etc Precautions: In rats treated with carbamazepine for two years, the incidence of tumours of the liver was found to be increased. There is, however, no evidence to indicate that this observation has any significant bearing on the therapeutic use of the drug.

 



GLAXO LABORATORIES LTD
GRISOVIN TABLETS
Contain griseofulvin.

Use: The treatment of fungal infections of the skin, scalp, hair or nails where topical therapy is considered inappropriate or has failed.
Contra-indications, warnings etc
Precautions: Long term administration of high doses of griseofulvin with food has been reported to induce hepatomas in mice and thyroid tumours in rats but not hamsters. The clinical significance of these findings is not known.

 



HOECHST
LASILACTONE CAPSULES
Contain Frusemide and Spironolactone.

Use: In the treatment of resistant oedema where this is associated with secondary hyperaldosteronism; conditions include chronic congestive cardiac failure and hepatic cirrhosis.
Contra-indications, warnings, etc Carcinogenicity: Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not certain.

 



ICI PHARMACEUTICALS
ATROMID -S
Contains Clofibrate.

Use: In the treatment of severe hyperlipoproteinaemia where full investigation has been performed to define the abnormality.
Contra-indications, warnings, etc Clofibrate has been shown to produce liver tumours in rats and mice. The liver changes found in rodents have not been seen in other species, including sub-human primates and man. The relevance of this finding to man has not been established.

 



ICI PHARMACEUTICALS
NOLVADEX, NOLVADEX - D AND NOLVADEX - FORTE TABLETS
Containing Tamoxifen Citrate.
Use:The treatment of breast cancer and the treatment of anovulatory infertility.
Contra-indications, warnings, etc Gonadal tumours in mice and liver tumours in rats receiving tamoxifen have been reported in long-term studies. The clinical relevance of these findings has not been established.

 



ICI PHARMACEUTICALS
ZOLADEX
Containing goserelin acetate.

Use: 1. Prostate cancer.
2. Advanced breast cancer in pre- and peri-menopausal women suitable for hormonal manipulation.
3. Endometriosis.
Contra-indications, warnings, etc - General: Following long-term repeated dosing with Zoladex, an increased incidence of benign pituitary tumours has been observed in male rats. Whilst this finding is similar to that previously noted in this species following surgical castration, any relevance to man has not been established.
In mice, long term repeated dosing with multiples of the human dose produced histological changes in some regions of the digestive system manifested by pancreatic islet cell hyperplasia and a benign proliferative condition in the pyloric region of the stomach, also reported as a spontaneous lesion in this species. The clinical relevance of these findings is unknown.

 



LEDERLE LABORATORIES
NOVANTRONE INJECTION
Contains mitozantrone hydrochloride.

Use: For the treatment of advanced breast cancer, non-Hodgkin's lymphoma and adult acute non-lymphocytic leukaemia. Novantrone has also been used in the palliation of non-resectable primary hepatocellular carcinoma.
Contra-indications, warnings, etc - Warnings: Novantrone is mutagenic in vitro and in vivo in the rat. In the same species there was a possible association between administration of the drug and development of malignant neoplasia. The carcinogenic potential in man is unknown.

 



LEDERLE LABORATORIES
PROSTAP SR
Contains leuprorelin acetate.

Use: In the treatment of advanced prostatic cancer and the management of endometriosis, including pain relief and reduction of endometriotic lesions.
Contra-indications, warnings, etc Warnings: Men: Whilst the development pituitary adenomas has been noted in chronic toxicity studies at high doses in some animal species, this has not been observed in long term clinical studies with Prostap.

 



LEDERLE LABORATORIES
THIOTEPA
Contains Thiotepa (N,N',N'' triethylenethiophosphoramide)

Use: A polyfunctional alkylating agent used alone or in combination with other cytotoxic drugs, hormones, radiotherapy or surgery in the treatment of neoplastic diseases.
Contra-indications, warnings, etc Thiotepa has been reported to possess mutagenic activity on the basis of bacterial, plant and mammalian mutagenicity tests. It has also been reported to be carcinogenic in mice and rats. These effects are consistent with its activity as an alkylating agent. The carcinogenic potential in humans has not been clearly established.

 



ELI LILLY & COMPANY LTD
CELANCE
Contains pergolide base.

Use: Adjunctive treatment to levodopa in the management of the signs and symptoms of Parkinson's disease.
Contra-indications, warnings, etc Carcinogenesis, mutagenesis and impairment of fertility: Two year carcinogenicity studies in mice and rats used doses up to 340 and 12 times the maximum human oral dose (6 mg or 6000 micrograms/day equivalent to 120 micrograms/kg/day). A low incidence of uterine neoplasms occurred in both rats and mice. Endometrial adenomas and carcinomas were observed in rats. Endometrial sarcomas were observed in mice. These occurrences are probably attributable to the high oestrogen/progesterone ratio, which would occur in rodents as a result of the prolactin-inhibiting action of pergolide mesylate. These endocrine mechanisms are not present in humans. However, there are no human data with pergolide to substantiate this conclusion concerning the lack of potential for human risk.
Mutagenic potential was evaluated in a battery of tests. A weak response was noted in one test but the other 3 tests were negative. The relevance to humans is unknown.

 



ELI LILLY & COMPANY LTD
SECONAL SODIUM
Contains Secobarbitone Sodium.

Use: For the short-term treatment of severe, intractable insomnia.
Contra-indications, warnings, etc Carcinogenesis: Animal data show that phenobarbitone can be carcinogenic after lifetime administration.

 



ELI LILLY & COMPANY LTD
SODIUM AMYTAL INJECTION
Contains Amylobarbitone Sodium.

Use: May be used parenterally to control status epilepticus, but it is not the barbiturate of choice in the routine treatment of grand mal epilepsy.
Contra-indications, warnings, etc Carcinogenesis: Animal data show that phenobarbitone can be carcinogenic after lifetime administration.

 



MARION MERRELL DOW LTD
DESTOLIT
Contains ursodeoxycholic acid.

Use: For the dissolution of radiolucent (i.e. non-radio opaque) cholesterol gallstones in patients with a functioning gallbladder.
Contra-indications, warnings, etc A product of this class has been found to be carcinogenic in animals. The relevance of these findings to the clinical use of ursodeoxycholic acid has not been established.

 



MARION MERRELL DOW LTD
SABRIL TABLETS
Contains vigabatrin.

Use: For the treatment of epilepsy which is not satisfactorily controlled by other antiepileptic drugs.
Contra-indications, warnings, etc Warning: Animal safety studies indicate that vigabatrin causes intramyelinic oedema in the brain white matter tracts. Currently there is no evidence to suggest that this effect occurs in man.

 



THOMAS MORSON PHARMACEUTICALS
DOLOBID
Contains Diflunisal.

Use: For the relief of pain and also inflammation associated with osteoarthritis and rheumatoid arthritis.
Contra-indications, warnings, etc Precautions: In rats and dogs, high oral doses of diflunisal (50-200 mg/kg/day) as with aspirin, produced similar pathological changes (gastro-intestinal ulceration and renal papillary oedema). These dosages are approximately 3 to 12 times the maximum dosages recommended in man.

 



ORTHO
ORTHO DIENOESTROL CREAM
Contains Dienoestrol.

Use: Atrophic vaginitis and kraurosis vulvae in post menopausal women, and for the treatment of pruritus vulvae and dyspareunia when associated with the atrophic vaginal epithelium.
Contra-indications, warnings, etc - ...long term continuous administration of natural and synthetic oestrogens in certain animal species increases the frequency of carcinomas of the breast, cervix, vagina and liver. There is now evidence that oestrogens increase the risk of carcinoma of the endometrium in humans. At the present time there is no satisfactory evidence that oestrogens given to post-menopausal women increase the risk of cancer of the breast, although a recent long-term follow up of a single physician has raised this possibility. However, because of animal data there is a need for caution in prescribing oestrogens for women with a strong family history of breast cancer or who have breast nodules, fibrocystic disease, or abnormal mammograms.
(Author's Note: Do oestrogens only increase the risk of cancer in female animals who have a strong family history of breast cancer, or who have breast nodules, fibrocystic disease or abnormal mammograms?)

 



ORTHO
RETIN-A LOTION, GEL, CREAM
Contains Tretinoin.

Use: For topical application in the treatment of acne vulgaris in which comedones, papules and pustules predominate.
Contra-indications, warnings, etc - Recent studies in mice treated with the active ingredient (tretinoin) of Retin-A and exposed to artificial sunlight suggest that tretinoin may speed up the appearance of sunlight induced skin tumours. Laboratory mice treated with tretinoin but not exposed to sunlight did not develop skin tumours. The significance of these studies as related to human beings is unknown. High oral doses of tretinoin (retinoic acid), like Vitamin A, are teratogenic in animals.

 



PARKE-DAVIS RESEARCH LABORATORIES
LOPID
Contains gemfibrozil and polysorbate 80 PhEur.

Use: For the primary prevention of coronary heart disease in men between 40-55 years of age and with hyperlipidaemias who have not responded to diet and other appropriate measures.
Contra-indications, warnings, etc Precautions: Long-term toxicity studies in rats and mice were carried out at one and ten times the human dose on a weight for weight basis. In male rats receiving ten times the human dose, there was a significant increase in incidence of benign liver nodules and liver carcinomas. Male rats receiving a dose equivalent to the human dose had no statistically significant increase in the incidence of liver carcinomas. At all dose levels, there were no statistically significant differences from controls in the incidence of liver tumours in female rats, or in mice of either sex.
Electron microscopy demonstrated a marked hepatic peroxisome proliferation following Lopid administration to the male rat. Similar changes have been sought but not found in the human liver at up to 27 months continuous gemfibrozil therapy.
Male rats had a dose-related increase of benign Leydig cell tumours. Subcapsular bilateral cataracts occurred in 10%, and unilateral cataracts in 6.3% of the high dose males.

 



PFIZER LTD
MITHRACIN
Contains plicamycin, mannitol and disodium phosphate.

Use: For the treatment of refractory hypercalcaemia associated with a variety of neoplasms.
Contra-indications, warnings, etc - Warnings: Antineoplastic and cytotoxic agents have been shown to be mutagenic and carcinogenic in animals and possibly man. Only limited animal and in vitro mutagenicity studies have been carried out with plicamycin; the possibility that plicamycin has similar effects to other antineoplastic cytotoxic agents should be borne in mind.

 



RHONE-POULENC RORER LTD
CALCITARE
Contains Calcitonin (Pork).

Use: For short term treatment in
i) Paget's disease of bone
ii) Hypercalcaemia.
Contra-indications, warnings, etc - A species and strain-specific dose-related increase of pituitary adenomas has been observed in long term toxicity studies in the rat. As the significance of these findings to man is uncertain, long term use is not recommended.

 



RHONE-POULENC RORER LTD
CALSYNAR
Contains synthetic Salmon Chloride. The solution also contains Sodium Chloride, Sodium Acetate, Acetic Acid and Phenol.

Use: For the short term treatment of:
a) Paget's disease of bone.
b) Advancing osteolytic hypercalcaemia of malignancy.
c) Pain associated with advanced metastatic bone cancer.
d) Postmenopausal osteoporosis.
Contra-indications, warnings, etc - Precautions: Rat carcinogenicity studies have shown a dose related excess of pituitary tumours. As the significance of this finding is uncertain, long term use is not recommended.

 



ROCHE PRODUCTS LTD
ROACCUTANE
Contains isotretinoin.

Use: For the treatment of cystic and conglobate acne and severe acne which has failed to respond to an adequate course of a systemic antimicrobial agent.
Contra-indications, warnings, etc - Precautions: At the completion of a lifespan study in rats there was an increased incidence of phaeochromocytoma in animals given isotretinoin at dosages of 32 and 8 mg/kg/day, but not 2 mg/kg/day. Since rats are particularly prone to develop this tumour type, the significance of this finding for use of Roaccutane in man is uncertain; nevertheless, repeated courses of treatment are not normally recommended.

 



SANOFI WINTHROP
NEGRAM
Contains Nalidixic Acid.

Use: For the treatment of acute or chronic infections.
Contra-indications, warnings, etc - Nalidixic acid has been shown to induce lesions in weight-bearing joints of young animals. The relevance of this to man is unknown.

 



SCHERING HEALTH CARE
ANDROCUR
Contains cyproterone acetate.

Use: Control of libido in severe hypersexuality and/or sexual deviation in the adult male.
Contra-indications, warnings, etc - Warnings/side-effects: Cyproterone acetate has been found to cause liver abnormalities in animals, including the development of tumours.

 



SCHERING HEALTH CARE
CYPROSTAT
Contains cyproterone acetate.

Use: Palliative treatment of prostatic carcinoma.
Contra-indications, warnings, etc - Cyproterone acetate has been found to cause liver abnormalities in animals, including the development of tumours.

 



SCHERING HEALTH CARE
DIANETTE
Contains anti-androgen cyproterone acetate and oestrogen ethinyloestradiol.

Use: In women only: a) severe acne, refractory to prolonged oral antibiotic therapy and b) idiopathic hirsutism of mild to moderate degree.
Contra-indications, warnings, etc - Warnings: Like many other steroids, cyproterone acetate, when given in very high doses and for the majority of the animal's life-span, has been found to cause an increase in the incidence of tumours, including carcinoma, in the liver of rats. The relevance of this finding to humans is unknown. Dianette has been shown to have good liver tolerance in women given prolonged treatment.

 



SEARLE
ALDACTIDE
Contains Spironolactone and Hydroflumethiazide.

Use: Congestive cardiac failure.
Contra-indications, warnings, etc - Warnings: Carcinogenicity: Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not certain.

 



SEARLE
CYTOTEC
Contains misprostol

Use: for the healing of duodenal ulcer and gastric ulcer including those induced by non steroidal anti inflammatory drugs (NSAID) in arthritic patients at risk, whilst continuing their NSAID therapy.
Further information: Cytotec in multiples of the recommended therapeutic dose in animals has produced gastric mucosal hyperplasia. This characteristic response of E prostaglandins reverts to normal on discontinuation of the compound. In patients, histological examination of gastric biopsies taken before and after treatment with misoprostol after up to one year's duration have shown no adverse tissue response attributable to misoprostol.

 



SEARLE
NAPRATEC
Contains Naproxen and Cytotec (containing misoprostol)
Uses: Naproxen is indicated for the treatment of rheumatoid arthritis, osteoarthritis (degenerative arthritis) and ankylosing spondylitis. Cytotec is indicated for the prophylaxis of nonsteroidal anti-inflammatory drug induced gastroduodenal ulceration.
Further information: Cytotec in multiples of the recommended therapeutic dose in animals has produced gastric mucosal hyperplasia. This characteristic response of E prostaglandins reverts to normal on discontinuation of the compound. In patients, histological examination of gastric biopsies taken before and after treatment with misoprostol after up to one year's duration have shown no adverse tissue response attributable to misoprostol.

 



E.R. SQUIBB & SONS LTD
DOLMATIL TABLETS
Contains sulpiride (and hydrated silica, lactose, magnesium stearate, methyl cellulose, potato starch, talc).

Use: Acute and chronic schizophrenia.
Contra-indications, warnings, etc - Warnings: In long term animal studies with neuroleptic drugs, including sulpiride, an increased incidence of various endocrine tumours (some of which have occasionally been malignant) has been seen in some but not all strains of rats and mice studied. The significance of these findings to man is not known; there is no evidence of an association between Dolmatil use and tumour risk in man.

 



THAMES LABORATORIES LTD
CHENOFALK
Contains chenodeoxycholic acid (CDCA). (And gluten).

Use: Dissolution of radiolucent gallstones measuring up to 15 mm diameter.
Contra-indications, warnings, etc - Warnings: Chenodeoxycholic acid given in long-term studies at doses of 600 mg/kg/day to rats and 1000 mg/kg/day to mice, induced malignant liver cell tumours in female rats and benign liver cell tumours in female rats and male mice. The clinical significance of these findings is not known.

 



THAMES LABORATORIES LTD
URSOFALK
Contains ursodeoxycholic acid (UDCA) and gluten.

Use: Dissolution of radiolucent gallstones measuring up to 15 mm diameter.
Contra-indications, warnings, etc - A product of this class has been found to be carcinogenic in animals. The relevance of these findings to the clinical use of UDCA has not been established.

 



TILLOTTS LABORATORIES
SULPITIL
Contains sulpiride.

Use: For the treatment of acute and chronic schizophrenia.
Contra-indications, warnings, etc - Warnings and precautions: In long term animal studies with neuroleptic drugs, including sulpiride, an increased incidence of various endocrine tumours, some of which have occasionally been malignant, has been seen in some, but not all, strains of rats and mice studied. The significance of these findings to man is not known. There is no current evidence of an association between neuroleptic use and tumour risk in man.

 



UPJOHN LTD
DEPO-PROVERA
Contains medroxyprogesterone acetate.

Use: Progestogen: for the treatment of endometriosis.
Contra-indications, warnings, etc Warnings, precautions, side-effects: Endometrial tumours have developed in monkeys given fifty times the human contraceptive dose but the relevance of this to man has not been established.

 



UPJOHN LTD
HEMABATE STERILE SOLUTION
Contains carboprost as the tromethamine salt.

Use: Treatment of post-partum haemorrhage due to uterine atony and refractory to conventional methods of treatment with oxytocic agents and ergometrine used either alone or in combination.
Contra-indications, warnings, etc - Precautions: Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone.

 



UPJOHN LTD
PROSTIN E2
Contains dinoprostone.

Use: Oxytocic agent. For the induction of labour when there are no foetal or maternal contra-indications.
Contra-indications, warnings, etc Precautions: Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone.

 



WELLCOME MEDICAL DIVISION
MYLERAN TABLETS
Contains Busulphan.

Use: For the palliative treatment of the chronic phase of chronic granulocytic leukaemia.
Contra-indications, warnings, etc - Precautions: Busulphan has been shown to be mutagenic in various systems, including bacteria, fungi, Drosophila and cultured mouse lymphoma cells. In vivo cytogenetic studies in rodents have shown an increased incidence of chromosome abberations in both germ cells and somatic cells after busulphan treatment.
Busulphan interferes with spermatogenesis in experimental animals.

 



WELLCOME MEDICAL DIVISION
RETROVIR CAPSULES AND SYRUP
Contains zidovudine.

Use: For the management of patients with advanced HIV disease.
Contra-indications, warnings, etc - Mutagenicity: Zidovudine was weakly mutagenic in a mouse lymphoma cell assay and was positive in an in vitro cell transformation assay. Clastogenic effects (chromosome damage) were observed in an in vitro study in human lymphocytes and in in- vivo oral repeat dose micronucleus studies in rats and mice. An in vivo cytogenetic study in rats did not show chromosomal damage. The clinical significance of these findings is unclear.
Carcinogenicity: Zidovudine was administered orally at three dosage levels to separate groups of mice and rats (60 females and 60 males in each group). Initial single daily doses were 30, 60 and 120 mg/kg/day and 80, 220 and 600 mg/kg/day in mice and rats respectively. The doses in mice were reduced to 20, 30 and 40 mg/kg/day after Day 90 because of treatment-related anaemia, whereas in rats only the high dose was reduced (to 450 and then 300 mg/kg/day on Days 91 and 279, respectively).
In mice, seven late-appearing (after 19 months) vaginal neoplasms (5 squamous cell carcinomas, one squamous cell papilloma and one squamous cell polyp) occurred at the highest dose. One late-appearing squamous cell papilloma occurred in the vagina of a middle-dose animal. No vaginal tumours were found at the lowest dose.
In rats, two late-appearing (after 20 months) vaginal squamous cell carcinomas occurred in animals given the highest dose. No vaginal tumours occurred at the middle or low doses in rats.
The predictive value of rodent carcinogenicity studies for humans is uncertain and thus the clinical significance of these findings is unclear.

***

In addition to the general warnings I have recorded above there are many drug companies which warn doctors not to give specific products to patients who are pregnant. These companies invariably report having performed experiments on pregnant animals but then often go on to admit (something like): `the relevance of these studies to human beings is not known'. (It is difficult to avoid asking the question: `Why do the studies if the relevance is not known?' A huge number of drug companies seem to be doing animal tests without knowing their relevance to human patients.) On other occasions drug companies report that animal experiments have shown that their drugs cause problems - but that human experience suggests that the drug is entirely safe so the animal experiments can be safely ignored! Animal experiments provide answers for all seasons. It is not surprising that drug companies love them.

In some of the examples which follow drug companies seem uncertain about the significance of the animal experiments which have been done. If the relevance of the animal experiments is not known or the experiments cannot be relied upon then why on earth does anyone do them? (Just as puzzling are the many instances where drug companies state that animal experiments have not indicated that there will be any problems if their drugs are given to pregnant women - but still advise doctors against giving those drugs to pregnant women!) These short sections are intended only to illustrate the point I want to make and are not intended to provide useful information about the drugs concerned.

 



ABBOTT LABORATORIES LTD
ENFLURANE

Use: An inhalation anaesthetic.
Use in pregnancy: Reproduction studies have been performed in rats and rabbits. Following single and multiple maternal administrations, no evidence of teratogenicity due to enflurane was found in the developing foetuses in these species. The relevance of these studies to the human is not known.

 



ABBOTT LABORATORIES LTD
ISOFLURANE

Use: An inhalation anaesthetic.
Use in pregnancy: Reproduction studies have been carried out on animals after repeated exposure to anaesthetic concentrations of Isoflurane. Studies with the rat demonstrated no effect on fertility, pregnancy, or delivery or on the viability of the offspring. No evidence of teratogenicity was revealed. Comparable experiments in rabbits produced similar negative results. The relevance of these studies to the human is not known.

 



ALCON LABORATORIES (U.K.) LTD
BETOPTIC
Contains betaxolol hydrochloride.

Use: For the reduction of elevated intra-ocular pressure in patients with ocular hypertension and chronic open-angle glaucoma.
Use in pregnancy: Although animal studies have not demonstrated any specific hazard there are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response this drug should be used during pregnancy only if clearly indicated.

 



ALCON LABORATORIES (U.K.) LTD
TOBRALEX
Contains Tobramycin.

Use: In the treatment of external bacterial conditions of the eye and its appendages.
Use in pregnancy: Reproduction studies in animals at doses up to thirty-three times the normal human systemic dose have revealed no evidence of impaired fertility or harm to the foetus due to tobramycin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

 



ALPHA THERAPEUTIC UK LTD
FLUOSOL
Contains perfluorodecalin (Perfluamine INN), and perfluorotri-n-propylamine (Perfluamine INN).

Use: During percutaneous transluminal coronary angioplasty to reduce or prevent intraprocedural myocardial ischaemia.
Use in pregnancy: Reproduction studies have been performed in rats at approximately three times the human dose and have revealed no evidence of impaired fertility or harm to the foetus due to Fluosol. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

 



ASTRA PHARMACEUTICALS LTD
PULMICORT
Contains budesonide and sorbitan trioleate and chlorofluorocarbons.

Use: For bronchial asthma.
Use in pregnancy: In pregnant animals, administration of budesonide causes abnormalities of foetal development. The relevance of this finding to man has not been established.

 



ASTRA PHARMACEUTICALS LTD
RHINOCORT
Contains budesonide, sorbitan trioleate and chlorofluorocarbons.

Use: Seasonal and perennial, allergic rhinitis and vasomotor rhinitis.
Use in pregnancy: In pregnant animals, administration of budesonide causes abnormalities of foetal developments. The relevance of this to man has not been established.

 



BAYER UK LTD
CANESTEN TOPICAL PRODUCTS
Contains clotrimazole BP.

Use: A broad spectrum antifungal.
Use in pregnancy: In animal studies clotrimazole has not been associated with teratogenic effects but following oral administration of high doses to rats there was evidence of foetotoxicity. The relevance of this effect to topical application in humans is not known. However, clotrimazole has been used in pregnant patients for over a decade without attributable adverse effects.

 



BAYER UK LTD
CANESTEN HC
Contains clotrimazole and hydrocortisone.

Use: A broad spectrum antifungal.
Use in pregnancy: Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of this to humans has not been established.
In animal studies clotrimazole has not been associated with teratogenic effects but following oral administration of high doses to rats there was evidence of foetotoxicity. The relevance of this effect to topical application in humans is not known. However, clotrimazole has been used in pregnant patients for over a decade without attributable adverse effects.

 



BAYER UK LTD
NYSTAFORM - HC OINTMENT/CREAM
Contains nystatin, chlorhexidine acetate, hydrocortisone.

Use: In infected dermatoses where fungal (particularly monilial) and/or bacterial infection is present.
Use in pregnancy: topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of this finding to humans has not been established.

 



BERK PHARMACEUTICALS LTD
BERKAPRINE
Contains Azathioprine.

Use: Facilitates the survival and function of organ transplants.
Use in pregnancy: Although it has been shown to be teratogenic in laboratory animals clinical evidence suggests that the risk is not appreciable in man.

 



BRISTOL-MYERS PHARMACEUTICALS
SOTAZIDE
Contains sotalol hydrochloride and hydrochlorothiazide.

Use: In the management of mild or moderate hypertension.
Use in pregnancy: In animal studies Sotazide has been shown to have no adverse teratogenic effects in doses up to 25 times the recommended human dose. However, its safe use in human pregnancy has not been fully established.

 



BRISTOL-MYERS PHARMACEUTICALS
TOLERZIDE
Contains sotalol hydrochloride and hydrochlorothiazide.

Use: In the management of mild or moderate hypertension particularly where a gradual fall in blood pressure is indicated such as in the elderly.
Use in pregnancy: In animal studies Tolerzide has been shown to have no adverse teratogenic effects in doses up to 50 times the recommended human dose. However its safe use in human pregnancy has not been fully established.

 



BROCADES
LOCOID C CREAM/OINTMENT
Contains hydrocortisone 17-butyrate and chlorquinaldol.

Use: The products are recommended for clinical use in the treatment of conditions responsive to topical corticosteroids, e.g. eczema, dermatitis and psoriasis, where secondary bacterial or fungal infection by a microorganism susceptible to chlorquinaldol is present or is to be prevented.
Use in pregnancy: In pregnant animals, administration of corticosteroids can cause abnormalities of foetal development. The relevance of this finding to human beings has no been established.

 



CHARWELL PHARMACEUTICALS LTD
MIGRALEVE
Contains buclizine hydrochloride, paracetamol and codeine phosphate.

Use: For the treatment of migraine attacks which can include the symptoms of migraine headache, nausea and vomiting.
Use in pregnancy: Migraleve has been in wide use for many years without apparent ill consequence. Although experiments in some species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose. Whilst there are no specific reasons for contra-indicating Migraleve during pregnancy, as with all drugs it is recommended that Migraleve be used in pregnancy only when the physician has considered the need in respect of the patients' welfare.

 



CILAG LTD
GYNO-PEVARYL CREAM
Contains econazole nitrate.

Use: For the treatment of vulvitis associated with candidal vaginitis. Balanitis.
Use in pregnancy: In animals econazole nitrate has shown no teratogenic effects, but is foetotoxic at high doses. The significance of this to man is unknown as there is no evidence of increased risk when taken in human pregnancy.

 



CILAG LTD
PEVARYL TC CREAM
Contains econazole nitrate and triamcinolone acetonide.

Use: For the topical treatment of inflammatory dermatomycoses and inflammatory skin conditions complicated by or threatened by bacterial or fungal skin infection.
Use in pregnancy: Topical administration of corticosteroids to pregnant animals can cause foetal abnormalities. The relevance of this finding to human beings has not been established.

 



CP PHARMACEUTICALS LTD
ARTHROXEN
Contains Naproxen.

Use: For the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout, and acute musculoskeletal disorders.
Use in pregnancy: There is inadequate evidence of safety of the drug in human pregnancy. As with other drugs of this type naproxen delays parturition in animals but the relevance of this finding to human patients is not known.

 



DISTA PRODUCTS LTD
ILOSONE
Contains erythromycin estolate.

Use: Antibiotic.
Use in pregnancy: Reproduction studies in rats, mice and rabbits, with doses several times the usual human dose, have revealed no evidence of impaired fertility or foetal harm related to erythromycin. There are no adequate studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

 



DISTA PRODUCTS LTD
KEFADOL
Contains cefamandole nafate.

Use: In the treatment of infections of the lower respiratory tract, genito-urinary tract, bones and joints, bloodstream (septicaemia), skin and soft tissue, gall bladder and peritoneum, and pelvic inflammatory disease in women, when due to susceptible micro-organisms.
Use in pregnancy: Reproduction studies in rats given doses of 500 or 1000 mg/kg/day (approximately 5 times the maximum clinical dose) revealed no evidence of impaired fertility or harm to the foetus due to cefamandole nafate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

 



DUPHAR LABORATORIES LTD
YUTOPAR
Contains ritodrine hydrochloride.

Use: The management of uncomplicated pre-term labour and/or foetal asphyxia in labour where it is desired to obtain uterine relaxation.
Use in pregnancy: Experiments in animals have shown that even in high dosage Yutopar has no teratogenic properties. Nevertheless, in view of the limited available information from human studies, the administration of Yutopar is not recommended during the first 16 weeks of pregnancy.

 



ICI PHARMACEUTICALS
FLUOTHANE
Contains 2-bromo-2-chloro-1,1,1-trifluoroethane stabilised with thymol.

Use: Fluothane is a volatile anaesthetic which is suitable for the induction and maintenance of anaesthesia for all types of surgery and in patients of all ages.
Use in pregnancy: Although the data from experimental investigations in animals cannot be directly related to man, it would be prudent to avoid general anaesthesia with inhalation agents during early pregnancy, except where such use is essential.

 



INVICTA PHARMACEUTICALS
CARDURA
Contains doxazosin mesylate.

Use: For the first-line treatment of hypertension and may be used as the sole agent to control blood pressure in the majority of patients.
Use in pregnancy: Although animal tests have shown no evidence of teratogenic effects, the clinical safety of Cardura during pregnancy has not yet been established.

 



INVICTA PHARMACEUTICALS
LUSTRAL
Contains sertraline hydrochloride.

Use: For the treatment of symptoms of depressive illness.
Use in pregnancy: Fertility studies conducted in rats at doses approximately 20 times the maximum human dose, indicated that sertraline had no adverse effects on fertility. There was, however, decreased neonatal survival following maternal administration of sertraline at doses approximately 5-6 times the maximum human dose. Similar effects on neonatal survival have been described for other antidepressant drugs.
Reproduction studies have been performed in rats and rabbits at doses up to 20 times the maximum daily human dose. There was no evidence of teratogenicity or embryotoxicity at any dose level. At the dose level corresponding to 5-6 times the maximum daily human dose, however, sertraline caused maternal toxicity which in turn delayed ossification processes in foetuses.
There are no adequate and well-controlled studies in pregnant women. Since animal reproduction studies are not always predictive of human response, Lustral should be used during pregnancy only if clearly needed.

 



JANSSEN PHARMACEUTICAL LTD
DAKTARIN ORAL GEL and DAKTARIN ORAL TABLETS Contains Miconazole base.

Use: Miconazole is a synthetic imidazole antifungal agent with a broad spectrum of activity against pathogenic fungi (including yeasts and dermatophytes) and Gram-positive bacteria (Staphylococcus and Streptococcus spp.).
Use in pregnancy: In animals, miconazole has shown no teratogenic effects but is foetotoxic at high oral doses. The significance of this to man is unknown.

 



JANSSEN PHARMACEUTICAL LTD
NIZORAL
Contains ketoconazole.

Use: Nizoral is an imidazole-dioxolane antimycotic which is effective after oral administration and has a broad spectrum of activity against dermatophytes, yeasts and other pathogenic fungi.
Use in pregnancy: When administered in high doses (over 80 mg/kg) to pregnant rats, Nizoral has been shown to cause abnormalities of foetal development. The relevance of this finding to humans has not been established, although Nizoral is contra-indicated in pregnancy.

 



KABI PHARMACIA
CALMURID HC
Contains carbamide (urea), hydrocortisone and lactic acid.

Use: Atopic eczema; Besnier's prurigo; acute and chronic allergic eczema; neurodermatitis and other hyperkeratotic skin conditions with accompanying inflammation.
Use in pregnancy: In pregnant animals, administration of corticosteroids can cause abnormalities of foetal development. The relevance of this finding to human beings has not been established.

 



LEDERLE LABORATORIES
LEDERCORT CREAM AND OINTMENT
Contains triamcinolone acetonide.

Use: In the treatment of inflammatory skin conditions such as atopic dermatitis; contact dermatitis; eczematous dermatitis; generalised erythrodermia; neurodermatitis; nummular eczema; otitis externa and seborrhoeic dermatitis.
Use in pregnancy: Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of this finding to human beings has not been established; however, topical steroids should not be used extensively in early pregnancy, i.e. in large amounts or for prolonged periods.

 



LEDERLE LABORATORIES
SUPRAX
Contains cefixime.

Use: For the treatment of the following acute infections when caused by susceptible micro-organisms:
Upper respiratory tract infections.
Lower respiratory tract infections.
Urinary tract infections.
Use in pregnancy: Reproduction studies have been performed in mice and rats at doses up to 400 times the human dose and have revealed no evidence of impairment fertility or harm to the foetus due to cefixime. In the rabbit, at doses up to 4 times the human dose, there was no evidence of a teratogenic effect; there was a high incidence of abortion and maternal death which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes in the population of the microflora of the intestine. There are no adequate and well-controlled studies in pregnant women. Suprax should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.

 



LEO LABORATORIES LTD
DICAPEN INJECTION
Contains sulbactam and ampicillin.

Use: For the treatment of infections caused by susceptible organisms.
Use in pregnancy: Animal reproduction studies have revealed no evidence of impaired fertility or harm to the foetus due to sulbactam and ampicillin. However, safety for use in human pregnancy and lactation has not been established.

 



LEO LABORATORIES LTD
FUCIBET CREAM
Contains betamethasone and fusidic acid.

Use: For the treatment of eczematous dermatoses including atopic eczema, infantile eczema, discoid eczema, contact eczema and seborrhoeic eczema when secondary bacterial infection is confirmed or suspected.
Use in pregnancy: Topical administration of any corticosteroid to pregnant animals can cause abnormalities of foetal development. The relevance of this finding to human beings has not been established; however, topical steroids should not be used extensively in pregnancy, i.e. in large amounts or for prolonged periods.

 



ELI LILLY & CO LTD
DOBUTREX
Contains dobutamine and sodium bisulphite.

Use: Dobutrex is indicated for adults who require inotropic support in the treatment of low output cardiac failure associated with myocardial infarction, open heart surgery, cardiomyopathies, septic shock and cardiogenic shock. Dobutrex can also increase or maintain cardiac output during positive end expiratory pressure (PEEP) ventilation.
Use in pregnancy: Reproduction studies performed in rats and rabbits have revealed no evidence of impaired fertility, harm to the foetus, or teratogenic effects due to dobutamine. As there are no adequate and well-controlled studies in pregnant women, and as animal reproduction studies are not always predictive of human response, dobutamine should not be used during pregnancy unless the potential benefits outweigh the potential risks to the foetus.

 



RHONE-POULENC RORER LTD
VALLERGAN
Contains trimeprazine tartrate.

Use: In urticaria and pruritus. Premedication for anaesthesia.
Use in pregnancy: There is inadequate evidence of the safety of Vallergan in human pregnancy, but it has been widely used for many years without apparent ill consequence. Some phenothiazines have shown evidence of harmful effects in animals.

 



ROCHE PRODUCTS LTD
FANSIDAR
Contains sulfadoxine and pyrimethamine.

Use: Treatment and prophylaxis of Plasmodium falciparum malaria.
Use in pregnancy: Foetal damage has been observed in the rat when any drug containing a folate inhibitor, including Fansidar, is administered in early gestation. The damage is caused by the folic acid antagonist, pyrimethamine, a component of Fansidar; the damage can be prevented by the concomitant administration of folinic acid.
However, no such adverse effects attributed to Fansidar have been reported during human clinical use, and the preparation is, therefore, not contra-indicated during pregnancy. The usual medical practice of avoiding the use of Fansidar during early pregnancy should be followed unless considered essential by a medical practitioner.

 



ROUSSEL LABORATORIES LTD
ACTINAC
Contains chloramphenicol, hydrocortisone acetate, butoxyethyl nicotinate, allantoin and precipitated sulphur.

Use: In the topical treatment of acne vulgaris and other acneiform conditions.
Use in pregnancy: In pregnant animals, administration of corticosteroids can cause abnormalities of foetal development. The relevance of this finding to human beings has not been established.

 



ROUSSEL LABORATORIES LTD
PROCTOSEDYL
Contains cinchocaine hydrochloride and hydrocortisone.

Use: For the short term relief (not more than 7 days) of pain, irritation and pruritus associated with haemorrhoids, pruritus ani.
Use in pregnancy: In pregnant animals, administration of corticosteroids can cause abnormalities of foetal development. The relevance of this finding to human beings has not been established.

 



ROUSSEL LABORATORIES LTD
SURGAM
Contains tiaprofenic acid.

Use: Rheumatoid arthritis, osteoarthritis; ankylosing spondylitis; low back pain; musculo-skeletal disorders such as fibrositis, capsulitis, epicondylitis and other soft-tissue inflammatory conditions; sprains and strains, post-operative inflammation and pain, and other soft-tissue injuries.
Use in pregnancy: Although animal studies have not revealed evidence of teratogenicity, safety in human pregnancy and lactation cannot be assumed and, in common with other non-steroidal anti-inflammatory agents, administration during the first trimester should be avoided.

 



SANOFI WINTHROP LTD
BIOGASTRONE
Contains carbenoxolone sodium and lactose.

Use: For the treatment of benign gastric ulcers in young and middle-aged patients, i.e those within the age range of 16 to 65 years.
Use in pregnancy: Although animal studies have shown no hazard, there is inadequate evidence of the safety of carbenoxolone in human pregnancy. Biogastrone should be avoided in patients who are pregnant.

 



SERVIER LABORATORIES LTD
NATRILIX
Contains indapamide hemihydrate.

Use: For the treatment of essential hypertension.
Use in pregnancy: No teratological effects have been seen in animals but because animal reproduction studies are not always predictive of human response, Natrilix should be used during pregnancy only if clearly needed.

 



SMITH KLINE & FRENCH LABORATORIES
STELAZINE
Contains trifluoperazine.

Use: A piperazine phenothiazine tranquilliser with potent antipsychotic, anxiolytic, and anti-emetic activity, and a pharmacological profile of moderate sedative and hypotensive properties, and fairly pronounced tendency to cause extrapyramidal reactions.
Use in pregnancy: Stelazine has been available since 1958. There are some animal studies that indicate a teratogenic effect, but results are conflicting. There is no clinical evidence (including follow-up surveys in over 800 women who had taken low-dosage Stelazine during pregnancy) to indicate that trifluoperazine has a teratogenic effect in man.

 



SMITH KLINE & FRENCH LABORATORIES
VERTIGON SPANSULE CAPSULES
Contains prochlorperazine.

Use: In the short term symptomatic treatment of vertigo due to Meniere's disease, labyrinthitis or other causes; nausea and vomiting associated with vertigo or other causes; and as an adjunct in the short term management of anxiety states.
Use in pregnancy: Prochlorperazine has been widely used for many years without apparent deleterious effects in pregnancy. There is however evidence of harmful effects in animals.

 



E. R. SQUIBB & SONS LTD
ECONACORT CREAM
Contains econazole nitrate and hydrocortisone.

Use: For the topical treatment of inflammatory dermatoses where infection by susceptible organisms co-exists.
Use in pregnancy: Topical administration of corticosteroids to pregnant animals can cause foetal abnormalities. The relevance of this finding to humans has not been established.

 



E.R. SQUIBB & SONS LTD
HALCIDERM TOPICAL
Contains halcinonide.

Use: In acute and chronic corticosteroid-responsive conditions including psoriasis and eczema.
Use in pregnancy: Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of this finding to humans has not been established.

 



E. R. SQUIBB & SONS
TRI-ADCORTYL CREAM/OINTMENT AND OTIC OINTMENT
Contains triamcinolone acetonide, neomycin, gramicidin and nystatin.

Use: The topical treatment of superficial bacterial infections, cutaneous candidosis and dermatological conditions known to respond to topical steroid therapy when threatened or complicated by bacterial or candidal superinfections. These include eczema and psoriasis.
Use in pregnancy: Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of this finding to humans has not been established.

 



STAFFORD-MILLER LTD
COLIFOAM
Contains hydrocortisone acetate.

Use: For the topical treatment of ulcerative colitis, proctosigmoiditis and granular proctitis.
Use in pregnancy: Systemic and topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. The relevance of this finding to human beings has not been established, but at present steroids should not be used extensively in pregnancy, that is in large amounts or for prolonged periods.

 



STAFFORD-MILLER LTD
QUELLADA LOTION
Contains gamma benzene hexachloride.

Use: For the treatment of scabies and body lice infestation.
Use in pregnancy: At very high doses foetal toxicity has been demonstrated in animals (rats and dogs). Quellada Lotion has been in wide use for many years without apparent ill consequence.

 



UPJOHN LTD
DALACIN T TOPICAL SOLUTION/LOTION
Contains clindamycin phosphate.

Use: Treatment of acne vulgaris.
Use in pregnancy: Safety for use in pregnancy has not been established.
Reproduction studies have been performed in rats and mice using subcutaneous and oral doses ranging from 100 to 600 mg/kg/day and have revealed no evidence of impaired fertility or harm to the foetus due to clindamycin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

 



WELLCOME MEDICAL DIVISION
LYCLEAR CREME RINSE
Contains permethrin and isopropanol.

Use: For the treatment of infections with the head louse Pediculus humanus capitis.
Use in pregnancy: Although animal reproductive studies have not revealed any evidence of impaired fertility or harm to the foetus from the administration of permethrin during pregnancy, they have shown that this compound crosses the placental barrier and is excreted in milk. Animal reproductive studies are not always predictive of the human response.

 



WELLCOME MEDICAL DIVISION
TRI-CICATRIN OINTMENT
Contains neomycin sulphate, bacitracin zinc, nystatin and hydrocortisone.

Use: For the topical treatment of eczema and dermatitis and intertriginous conditions in which bacterial or candidal infection is present or likely to occur.
Use in pregnancy: No specific studies have been conducted in pregnant patients although the active ingredients have been used topically for many years without evidence of adverse effects. The expected clinical benefit of treatment to the patient must be balanced against any possible, but unknown hazard to the developing foetus.
Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. Although the relevance of this finding to human beings has not been established, topical steroids should not be used extensively in pregnancy, i.e. in large amounts or for prolonged periods of time.

 



WELLCOME MEDICAL DIVISION
ZOVIRAX CREAM
Contains acyclovir.

Use: For the treatment of herpes simplex virus infections of the skin including initial and recurrent genital herpes and herpes labialis.
Use in pregnancy: Systemic administration of acyclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rats, rabbits or mice. Experience in humans is limited, so the clinical benefit to the patient must be balanced against any possible but unknown hazards to the developing foetus.
In a non-standard test in rats, foetal abnormalities were observed, but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.

 



WYETH LABORATORIES
ANTEPSIN TABLETS
Contains sucralfate.

Use: Tablets: For the treatment of duodenal ulcer, gastric ulcer and chronic gastritis.
Use in pregnancy: Teratogenicity studies in mice, rats and rabbits at doses up to 50 times the human dose have revealed no evidence of harm to the foetus. Safety in pregnant women has not been established and Antepsin should be used during pregnancy only if clearly needed.

 



WYETH LABORATORIES
ROBINUL INJECTION
Contains glycopyrrolate.

Use: 1. To protect against the peripheral muscarinic actions of anticholinesterases such as neostigmine and pyridostigmine, used to reverse residual neuromuscular blockade produced by nondepolarising muscle relaxants.
2. As a preoperative antimuscarinic agent to reduce salivary, tracheobronchial and pharyngeal secretions, and to reduce the acidity of the gastric contents.
3. As a preoperative or intra-operative antimuscarinic to attenuate or prevent intraoperative bradycardia associated with the use of suxamethonium or due to cardiac vagal reflexes.
Use in pregnancy: Although reproduction studies in rats and rabbits revealed no teratogenic effects from glycopyrrolate, safety in human pregnancy and lactation has not been established. Diminished rates of conception and of survival at weaning were observed in rats, in a dose-related manner. Studies in dogs suggest that this may be due to diminished seminal secretion which is evident at high doses of glycopyrrolate. The significance of this for man is not clear.

 



WYETH LABORATORIES
ROBINUL - NEOSTIGMINE INJECTION
Contains glycopyrrolate and neostigmine methylsulphate.

Use: Reversal of residual non-depolarising (competitive) neuromuscular block.
Use in pregnancy: Reproduction studies in rats and rabbits revealed no teratogenic effects from glycopyrrolate. Safety in human pregnancy and lactation has not been established. However, diminished rates of conception and of survival at weaning were observed in rats, in a dose-related manner. Studies in dogs suggest that this may be due diminished seminal secretion which is evident at high doses of glycopyrrolate. The significance of this for man is not clear.

***

With all this evidence available it is difficult to avoid the sad but inevitable conclusion that animal experiments are used because they are financially expedient. Animals are not just relatively cheap to use but there also are clear commercial advantages for the world's most successful and ruthless industry. The bizarre but inescapable conclusion is that drug companies depend on the fact that animal experiments are unreliable in order to get their new products onto the market without testing them properly. The very unreliability and unpredictably of animal experiments makes them valuable. Drug companies test on animals so that they can say that they have tested their drugs before marketing them. If the tests show that the drugs do not cause serious disorders when given to animals the companies say: `There you are! We have tested our drug - and have proved it to be safe!' If, on the other hand, tests show that a drug does cause serious problems when given to animals the companies say: `The animal experiments are, of course, unreliable and cannot be used to predict what will happen when the drug is given to humans. We have, however, tested our drug.' This double edged absurdity, which only works because of the enormous influence which the pharmaceutical industry holds over governments and regulatory authorities, and which would sound like a nightmare conjured up by a paranoid lunatic if it were not so easily proved, means that the industry never loses and patients never win.

(There is even evidence to show that drug companies will sometimes perform animal experiments on products made by other companies. The only reason I can think of for a company to do animal experiments on another company's products is to obtain results which might add to the confusion and suggest that a product may not be safe. It is always possible to obtain disturbing results if you give animals a high enough dose of a drug.)

In order to disguise the real (commercial) reasons for performing animal experiments drug companies will sometimes claim that they don't like doing animal experiments but do them because they are required to do so by the law. This is not true. There are, for example, no laws in Britain requiring animal experiments to be performed during drug testing. Drug companies say that they are required to perform animal experiments by the law. Government spokesmen say that it is drug companies who choose to do animal experiments in order to test the safety of their drugs.

***

Scientists outside the pharmaceutical industry support vivisection for several reasons. First, of course, animal experiments have now been used for so long and by so many scientists that thousands of reputations would be irrevocably shattered if it were accepted by the research industry that the work they have been doing for so many years was fatally flawed. Second, it is remarkably quick and simple to plan, research and write and publish scientific papers if you are using animals. Decent and useful research, involving human patients, is much harder to organise - and since most of the medical scientists using animals in experiments are not medically qualified most of them would not, in any case, be allowed to perform any sort of clinical research. Prolific publishing (usually accompanied by optimistic conclusions about the value of the research) is the best way to ensure a steady income from grants. It is the quantity not the quality of research which governs the financial results. The charities which pay for much of the animal research done want to be able to fill their annual reports with impressive and optimistic accounts of research in progress.

The second rate scientists who perform animal experiments outside the pharmaceutical industry are undoubtedly grateful to the industry for creating and maintaining the myths which support the milieu in which they work. And the industry in turn, recognising that the fact that universities still perform animal experiments supports the validity of THEIR work is also grateful: often commissioning highly paid research work from `independent' scientists in universities and colleges. In some universities whole departments are financed exclusively by the drug industry. The myth that animal experiments are of value to doctors and patients is sustained because the vast majority of doctors - the only people who could expose the absurd rigmarole for the sham that it is - are either uninterested in how drugs are tested (and apathetic about the dishonesty involved) or are so beholden to the industry that they are unwilling or unable to criticise it. The vast majority of the thousands of medical journals in existence rely to a greater or lesser extent on drug industry advertising to stay alive and so the editors of these journals are reluctant to publish anything critical of any aspect of the system as it operates.

Articles criticising the drug industry, the way drugs are tested or the use of animal experiments are rare. The existence of so many medical journals, largely sustained by drug company advertising, means that there is a steady and constant demand for new scientific papers. And so the whole system is self supporting. The industry needs to publish research papers in order to satisfy the regulatory authorities and to convince possibly sceptical doctors that their products have been well tested and proven to be both efficacious and safe. Independent researchers need to publish papers in order to provide the charities which fund their work with evidence with which to impress their subscribers and donors. And the journals need articles to publish.

Those who perform and defend animal experiments sometimes try to explain away the differences which exist between the results obtained when drugs are given to animals and when drugs are given to human beings by claiming that the dosages used when giving drugs to animals are too high. Strangely, they never bother to explain why they deliberately make the dosages they give so high as to be of no value. The truth is that no one does know how much of a drug to give to an animal in the hope of obtaining results which might be relevant to an animal (a human being) weighing a hundred or a thousand times as much and having entirely different physiological and anatomical systems.

The differences in results obtained when giving drugs to children and adults is so vast that paediatricians frequently complain when drug companies fail to perform special trials on children. Similarly, all good physicians know that adult human beings of different sizes and different ages may respond in different ways to the same drug. (There is something quite absurd about giving a 7 stone woman and a 20 stone man exactly the same dose of an antibiotic for example). Many drug companies now warn prescribers that special dosage rules must be followed when giving drugs to elderly patients.

It should, therefore, be clear to anyone with any knowledge of physiology that the only possible argument for trying out drugs on animals is in the hope that the tests will show signs of toxicity. However, even this hope is dashed because there is a huge amount of evidence available to show that animals frequently react quite differently to human beings when given drugs. A cat can't be expected to react the same way as a dog or a sheep or a cow or a mouse or a guinea pig or a rat or a human being when given a drug. Of course, the simple law of averages means that occasionally there will be results which seem of value - but how is anyone supposed to know which results to take notice of and which to ignore? Most doctors, even many who support vivisection, will confirm that animal experiments can be misleading. After the European Medical Journal published a survey showing that 88% of doctors agreed that animal experiments can be misleading because of anatomical and physiological differences between animals and humans the editor of the British Medical Journal wrote to say that he felt that most doctors would agree with the phrase that `laboratory experiments performed on animals can be misleading because of anatomical and physiological differences between animals and humans'. One eminent expert expressed his surprise that the survey did not find that 100% of the doctors who took part in the survey believed that animal experiments could be misleading. The problem, of course, is that no doctor can tell you which animal experiments are going to be most misleading.

If you test a drug on eight species of animal and the drug turns out to cause cancer in two of those animals, to cause liver problems in another two, to cause blindness in two more and to be quite safe in a final pair should you accept the results from the two that develop cancer, the two who develop liver problems, the two who become blind or the two who remain well?

In practice, of course, no one knows which results to accept and which to ignore and so all the results are ignored (as shown by the number of drugs currently freely available for doctors to prescribe which are known to cause serious problems in animals). The absurdity of the whole business of giving drugs to animals, and expecting to obtain useful results, is taken even further away from logic and practicality by the knowledge that animals in cages behave quite differently to animals in the wild and the understanding that since diet, exercise patterns and genetics all have significant effects on the way human beings respond to disease and drug therapy it is likely that these, or other influences, may also affect animals when they are given drugs.

I have concentrated in this chapter (and, indeed, in the whole of this book) on the uselessness of animal experiments designed to help doctors judge or evaluate new drugs. But animals are often used to `help' surgeons decide on the value of new surgical procedures and those who support and defend animal experimentation often claim that without animal experiments no progress would be made in surgery.

This is, of course, absolutely nonsense for as practising surgeons will readily confirm the differences between animal and human anatomy and physiology is so great that trying out new techniques on animals is worse than useless - and quite likely to lead to dangerous consequences.

Moreover, attempts to perform controversial or questionable operative procedures in animals (in an attempt to identify or quantify the risks with those procedures) have clearly been regarded by the medical establishment with contempt.

For example, even though experiments have shown that vasectomy operations accelerated arteriosclerosis in monkeys no one seems to have taken any notice of this discovery and several million vasectomy operations are still performed annually. No one knows which experiments, if any, can be regarded as providing useful information and so no experiments can possibly provide information which can be useful (except retrospectively!).

If we don't know which animal experiments are relevant then there is no point in doing any of them.

Copyright Vernon Coleman 1994

 

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