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Status:
US Approved Rx
(1990)
Source:
ANDA072759
(1990)
Source URL:
First approved in 1972
Source:
PAVULON by ORGANON USA INC
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Conditions:
Pancuronium (trademarked as Pavulon) is an aminosteroid muscle relaxant with various medical uses. Pancuronium is a typical non-depolarizing curare-mimetic muscle relaxant. It competitively inhibits the nicotinic acetylcholine receptor at the neuromuscular junction by blocking the binding of acetylcholine. It has slight vagolytic activity, causing an increase in heart rate, but no ganglioplegic (i.e., blocking ganglions) activity. It is a very potent muscle relaxant drug, with an ED95 of only 60 µg/kg body weight. The onset of action is relatively slow compared to other similar drugs, in part due to its low dose - an intubating dose takes 3–6 minutes for full effect. Clinical effects (muscle activity lower than 25% of physiological) last for about 100 minutes. The time needed for full (over 90% muscle activity) recovery after single administration is about 120–180 minutes in healthy adults. Pancuronium is used with general anesthesia in surgery for muscle relaxation and as an aid to intubation or ventilation. It does not have sedative or analgesic effects. Side-effects include moderately raised heart rate and thereby arterial pressure and cardiac output, excessive salivation, apnea and respiratory depression, rashes, flushing, and sweating. The muscular relaxation can be dangerous for the seriously ill and it can accumulate leading to extended weakness. Pancuronium is not preferable to long-term use in ICU-ventilated patients. Pancuronium is also used as one component of a lethal injection in the administration of the death penalty in some parts of the United States.
Status:
US Approved Rx
(1972)
Source:
NDA016968
(1972)
Source URL:
First approved in 1972
Source:
NDA016968
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Conditions:
Carbachol is a potent cholinergic (parasympathomimetic) agent which produces constriction of the iris and ciliary body resulting in reduction in intraocular pressure.
Status:
US Approved Rx
(2022)
Source:
ANDA213730
(2022)
Source URL:
First approved in 1972
Source:
NDA017105
Source URL:
Class (Stereo):
CHEMICAL (RACEMIC)
Conditions:
Clorazepate is a water-soluble benzodiazepine derivative effective in the treatment of anxiety. It has also muscle relaxant and anticonvulsant actions. Studies in healthy men have shown that clorazepate dipotassium has depressant effects on the central nervous system. clorazepate is a prodrug since orally administered it is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug. Nordiazepam positively modulates GABAA receptors to produce anxiolytic and anticonvulsant effects.
Status:
US Approved Rx
(1997)
Source:
NDA020475
(1997)
Source URL:
First approved in 1971
Source:
RETIN-A by VALEANT INTL
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Targets:
Conditions:
Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.
Status:
US Approved Rx
(1999)
Source:
ANDA075568
(1999)
Source URL:
First approved in 1968
Source:
NDA016324
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Conditions:
Azathioprine remains one of the most important and widely prescribed drugs for immunosuppression/immunomodulation in autoimmune disease over 30 years after its introduction. Azathioprine is licensed for the treatment of only a limited range of autoimmune disorders, which is probably a reflection on the age of the drug. Widening the license for a drug is both costly and time consuming, and it would make no commercial sense for manufacturers to do so, at this late stage of life, for azathioprine. However, azathioprine is now so well established as an immunomodulating drug in autoimmune disorders that it represents the gold standard by which other drugs are compared. Azathioprine is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. The combined use of azathioprine tablets with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects. The use of azathioprine tablets with these agents cannot be recommended. Azathioprine is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication. Azathioprine is metabolized to 6-mercaptopurine (6-MP). Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes and liver; no azathioprine or mercaptopurine is detectable in urine after 8 hours. Activation of 6-mercaptopurine occurs via hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and a series of multi-enzymatic processes involving kinases to form 6-thioguanine nucleotides (6-TGNs) as major metabolites.
Status:
US Approved Rx
(2018)
Source:
ANDA208805
(2018)
Source URL:
First approved in 1967
Source:
NDA016092
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Targets:
Ethacrynic acid is a monosulfonamyl loop or high ceiling diuretic. Ethacrynic acid acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Ethacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis. Ethacrynic acid inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. Diuretics also lower blood pressure initially by reducing plasma and extracellular fluid volume; cardiac output also decreases, explaining its antihypertensive action. Eventually, cardiac output returns to normal with an accompanying decrease in peripheral resistance. Its mode of action does not involve carbonic anhydrase inhibition. Ethacrynic acid is indicated for the treatment of high blood pressure and edema caused by diseases like congestive heart failure, liver failure, and kidney failure.
Status:
US Approved Rx
(1997)
Source:
ANDA074712
(1997)
Source URL:
First approved in 1966
Source:
ANDA074623
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is a disaccharide (double-sugar) formed from one molecule each of the simple sugars (monosaccharides) fructose and galactose. Lactulose is not normally present in raw milk but is a product of heat-processed: the greater the heat, the greater amount of this substance. Lactulose is not absorbed in the small intestine nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through osmosis leading to softer, easier to pass stool. It has a secondary laxative effect in the colon, where it is fermented by the gut flora, producing metabolites which have osmotic powers and peristalsis-stimulating effects (such as acetate), but also methane associated with flatulence. Lactulose is metabolized in the colon by bacterial flora to short chain fatty acids including lactic acid and acetic acid. These partially dissociate, acidifying the colonic contents (increasing the H+ concentration in the gut).[14] This favors the formation of the nonabsorbable NH+4 from NH3, trapping NH3 in the colon and effectively reducing plasma NH3 concentrations. Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment. Lactulose is used for chronic idiopathic constipation, i.e. chronic constipation occurring without any identifiable cause. Lactulose may be used to counter the constipating effects of opioids, and in the symptomatic treatment of hemorrhoids as a stool softener.
Status:
US Approved Rx
(1982)
Source:
NDA018667
(1982)
Source URL:
First approved in 1966
Source:
NDA016273
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Targets:
Conditions:
Furosemide, a sulfonamide-type loop diuretic structurally related to bumetanide, is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron. Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron, furosemide is a very potent diuretic. Furosemide is sold under the brand name Lasix among others.
Status:
US Approved Rx
(2017)
Source:
ANDA203385
(2017)
Source URL:
First approved in 1964
Class (Stereo):
CHEMICAL (ABSOLUTE)
Targets:
Conditions:
Dactinomycin (actinomycin D) was isolated from Streptomyces by Selman Waksman in 1940s. The antibiotic shows anti-cancer activity; it was approved by FDA for the treatment of different cancer conditions among which are Ewing's sarcoma, Wilm's tumor, gestational trophoblastic disease, etc. Dactinomycin exerts its action by binding to DNA (preferably to GC motif) and thus inhibiting transcription.
Status:
US Approved Rx
(1988)
Source:
ANDA071484
(1988)
Source URL:
First approved in 1963
Source:
ONCOVIN by LILLY
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Targets:
Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific. The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.Vincristine was marketed under the brand name Oncovin, but was discontinued. In 2012 the FDA approved a Liposomal formulation of Vincristine, named MARQIBO KIT.