Hydralazine Hydrochloride

Yellow crystals

White, crystalline powder

Very slightly soluble in ether and alcohol

In 95% ethanol, 0.2 g/100 ml

In water, 44.2 g/l @ 25 °C; 30.1 g/l @ 15 °C

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Vasodilator Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P233, P260, P261, P264, P264+P265, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P305+P351+P338, P308+P316, P318, P319, P321, P330, P332+P317, P337+P317, P342+P316, P362+P364, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 114 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl hydralazine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Acute Tox. 3 (100%)

Acute toxicity (Oral) - Category 3

Commercially available preparation of hydralazine hydrochloride should be stored at a temperature less than 40 °C, preferably at 15 to 30 °C; freezing of the injection should be avoided. Hydralazine hydrochloride tablets should be stored in tight, light-resistant containers.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

...The possibility exists that nialamide may prolong and intensify the antihypertensive action of hydralazine by inhibiting its metabolism and by an additive effect of interfering with adrenergic functional transmission.

One patient receiving both hydralazine and hexamethonium several times a day after bilateral sympathectomy for systemic hypertension developed a myopia of more than one diopter in definite association with the use of these drugs.

/Nonsteroidal antihypertensive drugs, especially indomethacin/ may reduce antihypertensive effects of hydralazine; indomethacin, and possibly other nonsteroidal anti-inflammatory drugs, may antagonize the antihypertensive effect by inhibiting renal prostaglandin synthesis and/or by causing sodium and fluid retention.

Antihypertensive effects may be potentiated when these medications /diazoxide or other hypotension-producing medications/ are used concurrently with hydralazine; concurrent use of diazoxide or other potent parenteral antihypertensives with hydralazine may result in a severe, additive hypotensive effect; although some antihypertensive and/or diuretic combinations are frequently used for therapeutic advantage, dosage adjustments may be necessary during concurrent use. Patients should be continuously observed for excessive fall in blood pressure for several hours after concurrent administration of diazoxide or other potent parenteral antihypertensives.

IDENTIFICATION: Hydralazine, hydralazine hydrochloride are antihypertension agents. Hydralazine is a white to off-white crystalline powder. It is odorless to almost odorless compound. Solubilities are: soluble in water, slightly soluble in ethanol and in methanol; practically insoluble in ether or chloroform. Hydralazine is used to treat arterial hypertension (primary; malignant; pulmonary; pre-eclampsia and eclampsia), congestive heart failure, pulmonary hypertension in chronic obstructive pulmonary disease, and aortic regurgitation. Some benefit may be seen if used in primary oesophageal motility disorders and psoriasis. Recent observations indicate that it can be used to withdraw patients from dobutamine in severe congestive heart failure. Infants with chronic heart failure and left-to-right shunts may experience some benefit with hydralazine use. HUMAN EXPOSURE: Main risks and target organs: Hypotension, sinus tachycardia, palpitations, sweating, flushing, and headache are the most commonly reported side effects. Severe hypotension may result in myocardial and/or cerebral ischemia. Congestive heart failure, peripheral neuropathy, paresthesia, hepatotoxicity, drug fever, nausea, vomiting and diarrhea are also possible side effects but are most commonly related to chronic use. A lupus-like syndrome may be seen in 15 per cent of patients taking 400 mg or more of hydralazine daily. A higher percentage of patients develop circulating antinuclear antibodies. This syndrome is less common in patients who receive less than 200 mg per day. The cardiovascular system is mainly affected by hydralazine. The nervous system, the liver, the gastrointestinal and the immunologic systems are also target organs. Summary of clinical effects: Signs and symptoms of poisoning depends on the dose taken and the time of exposure. These include severe hypotension, reflex tachycardia, palpitations, cardiac arrhythmias, syncope, sweating, cerebral and/or myocardial ischemia, headache and dizziness. Nausea, vomiting and diarrhoea are also observed. Hypokalemia and lactic acidosis can occur. Ten to twenty per cent of patients taking 400 mg or more of hydralazine can be affected by a lupus like syndrome. This effect is almost exclusively seen in slow acetylators. Chronic use may also lead to fluid retention, peripheral neuropathy and paresthesia. Bioavailability: Hydralazine bioavailability is variable, ranging from 50 to 90% of a single oral dose. Depending on the dose, peak plasma levels occur from 0.3 to 1.0 hour after a single oral dose. With increasing oral dose, there is a non-proportional increase in the hydralazine plasma levels. A saturation in the metabolic pathways (gut, liver) may be responsible for this phenomenon. Hydralazine undergoes first-pass metabolism which is determined by the acetylator phenotype. Therefore, different bioavailability patterns are expected: it is greater in slow acetylators than in fast acetylators. Food may interfere with hydralazine bioavailability. It has been demonstrated that plasma levels and area under the curve bioavailability is reduced up to 46 % if the drug is administered 45 minutes after a meal. Contraindications: With the exception of a history of systemic lupus erythematosis there are no absolute contraindications to hydralazine use if combined with an adrenergic blocker. Relative Contraindications: Hydralazine should be used cautiously in patients with dissecting aortic aneurysm, heart failure with high output, cor pulmonale or myocardial insufficiency caused by mechanical obstruction due to valvular diseases. It should also be used with caution in patients with coronary and/or cerebrovascular diseases because of increased ischemia. Renal failure requires dose adjustment despite the acetylator phenotype. In geriatric patients it is wise to start with lower doses (about one-half of the adult normal dose), with subsequent titration. Postural hypotension and other side effects are more common in older people. Routes of entry: Oral: Oral ingestion is most likely the most common route of poisoning. Parenteral: Poisoning may occur by intravenous administration. Parenteral therapy is recommended only when the oral route is not feasible. Absorption by route of exposure: By the oral route, hydralazine absorption is variable and ranges from 50 to 90 %. Bioavailability is greater in slow compared to fast acetylators. Increasing the dose, there is a non-proportional increase in the serum levels, possibly because of saturation in the metabolic pathways of hydralazine. Peak plasma levels are achieved in about 60 minutes after ingestion. The maximum hypotensive effect occurs from 2 to 4 hours after ingestion and may persist for up to 24 hours. Distribution by route of exposure: Binding to plasma proteins is reported to be greater than 87 %. Hydralazine can be found in high concentrations in liver, kidneys, lungs, adrenals and arteries. Biological half-life by route of exposure: Biological half-life is about 3 to 4 hours and is not related to the rate of acetylation. However, the half-life of its antihypertensive effect may last up to 100 hours. The effects may be prolonged with renal failure. Metabolism: Hydralazine undergoes first pass metabolism by acetylation which is genetically determined. The gastro-intestinal mucosa and the liver are the main sites of this saturable metabolic pathway. The major metabolites are: MTP; the acetylation product (3-methyl-1,2,4-triazolo-(3,4a)phtalazine); HPH hydralazine pyruvic acid hydrazone), which is the major plasma metabolite; N-AcHPZ (4-(2-acetylhydrazino) phthalazin-1-one, which is mostly found in the urine and 3-OHMTP (3-hydroxymethyl-1,2,4-triazolo(3,4a) phtalazine. Systemic metabolism is dependent on hydroxylation followed by conjugation with glucuronic acid in the liver, which is not dependent on the rate of acetylation. Therefore, the half-life does not differ very much between slow and fast acetylators. Biotransformation of xenobiotics containing an aromatic amine or a hydrazine group by N-acetylation is dependent on the N-acetyltransferases enzymes which in humans are expressed by only two different enzymes, known as NAT1 and NAT2. Genetic polymorphism determines a reduction in the activity/stability of the NAT2 enzyme which is observed in slow acetylators. Elimination by route of exposure: About 65% of the total dose is excreted in the urine in 24 hours. Slow acetylators eliminate 15 to 20% as N-AcHPZ and 10% as conjugated 3-OHMTP. In fast acetylators, 30% is excreted in the urine as N-AcHPZ, as well as 10 to 30% as conjugated 3-OHMTP. The fecal contend of hydralazine is about 10% of the dose. Mode of action: Toxicodynamics: Hydralazine is a potent arteriolar vasodilator by producing relaxation of vascular smooth muscle. The vasodilation is most marked in the splanchnic, coronary, cerebral and renal arterial beds. Some of the symptoms may be caused by vasodilation and histaminic effects. Iron chelation may lead to anemia. A hydralazine-DNA pyrimidine interaction resulting in immune responses to hydralazine and nuclear antigens in which antibodies to native DNA occur can explain the hydralazine-induced lupus erythematosis. Recent observations have demonstrated that in the presence of metal ions or peroxidase hydrogen peroxide, hydralazine increased free radical production and site specific DNA-damage. It was suggested that this could be a possible explanation for hydralazine induced lupus, mutation and cancer. Slow acetylators produce hydralazine degradation to phthalazine through the intermediate of nitrogen-centered free radical and carbon centered free-radicals. In human red blood cells, hydralazine increases hydrogen peroxide production and proteolysis has been noted. As far as the hydralazine-induced lupus syndrome is concerned, since it is a rheumatic and febrile disease, and as a collagen simulating disease, it has become evident that this syndrome is indistinguishable from that of systemic lupus erythematous. Since then, it has been confirmed by several observations that anti-nuclear antibodies are almost always seen in the patients affected with the disease. These antibodies may persists for up to nine years after hydralazine exposure. A relationship between the phenotype acetylator activity to the antinuclear antibodies production and toxic symptoms in hypertensive patients was demonstrated. Slow acetylator Caucasian people are at higher risk. Pharmacodynamics: The mechanism of action of the vasodilation induced by hydralazine is not yet well understood. Recent observations suggest that it inhibits calcium release of the vascular smooth muscle sarcoplasmic reticulum by blocking the inositol trisphosphate (IP3)-induced calcium release, therefore reducing calcium turnover inside the cell. The resultant vasodilation reduces cardiac afterload, increasing cardiac function in patients with heart failure. However, some evidence exists concerning a direct action in the myocardium by an increase in calcium influx through the sarcolemma. This may be partially due to the stimulation of the beta-adrenoreceptors. However, a study describing a large number of patients found no evidence that hydralazine alters the risk of gut and lung cancer. Hydralazine readily crosses the placental blood-barrier but has no effect on the placental circulation. It has minimal effects on isolated human umbilical vessels. Human data have demonstrated that there is no increased risk of congenital malformations in the offspring of women treated with hydralazine, even during the first trimester of pregnancy. Some cases of hydralazine-induced neonatal thrombocytopenia with increased risk of bleeding were reported to the Swedish. Interactions: Indomethacin may produce a clinically important decrease in the hypotensive effects of hydralazine, however, such effects have been demonstrated only in healthy volunteers. Some pharmacokinetic interactions have been described with the concomitant administration of hydralazine and beta-blockers. Increased bioavailability of propranolol, and of metoprolol were observed in these circumstances. This interaction was not seen with a sustained release preparation of propranolol. Pyridoxine can reverse the neuropathy produced by hydralazine. Severe hypotensive sequelae of combined diazoxide and hydralazine therapy was observed in some patients. Beta-blockers can reduce the side effects produced by sympathetic stimulation when hydralazine is clinically used to treat hypertension. However, when used in pregnancy associated with propranolol, some negative effects on fetal development may occur. These effects are not seen with the combination of pindolol and hydralazine. Combined with propranolol, there may be a reduction in the activity of lipoprotein lipase activity, and alteration of the lipid profile. Organic nitrates when associated with hydralazine may have beneficial effects in patients with long-standing mitral regurgitation. In patients with heart failure, the combination of hydralazine and dinitrate isosorbide has a better survival rate compared to placebo. Main adverse effects: Hypotension, syncope, headache, myocardial and/or cerebral ischemia, flushing, nasal congestion, angina pectoris, fluid retention, edema of the lower extremities, palpitations, tachycardia, nausea and vomiting. Myocardial infarction and sudden death can occur. Antinuclear antibodies and lupus-like syndrome may occur. ANIMAL/PLANT STUDIES: Combined with prenalterol, hydralazine exhibits a cardiotoxic effect by enhancing myocardial necrosis in rats. This effect could not be reproduced in rabbits. Carcinogenicity: Hydralazine has been associated with the appearance of lung carcinogenesis in mice. In mice and rabbits, hydralazine can produce skeletal malformations due to its effect on the collagen synthesis. When given to pregnant rats in doses non-toxic to the mother, hydralazine does not have teratogenic or fetotoxic effects. Mutagenicity: Hydralazine can induce structural and/or conformational changes in DNA. It has a clastogenic effect in the liver which can be the main target site of genotoxicity.

/HUMAN EXPOSURE STUDIES/ ...After a 2-wk, single-blind, placebo phase, 77 patients with essential hypertension were given active agent as monotherapy in a double-blind fashion for 8-20 weeks. The dose of each agent was titrated to achieve diastolic blood pressure <90 mm Hg. ...Total cholesterol decreased during therapy with hydralazine but increased in patients receiving the combination of lisinopril and /hydrochlorothiazide/ (HCTZ). /High-density lipoprotein/ (HDL) cholesterol was depressed in those taking HCTZ alone and in combination with lisinopril. /Low-density lipoprotein/ (LDL) cholesterol was lowered during therapy with hydralazine but was otherwise unaffected by all other agents. None of the agents evaluated significantly affected triglyceride concentrations. Thus, monotherapy with lisinopril, enalapril, and nitrendipine do not affect plasma lipid concentrations. ...

/HUMAN EXPOSURE STUDIES/ A pharmaceutical worker developed asthma when exposed to hydralazine, an antihypertensive drug. The diagnosis of occupational asthma was supported by specific inhalation challenges, which produced a late asthmatic reaction and an increase in bronchial responsiveness. No evidence of an IgE or an IgG dependent mechanism could be found.

/HUMAN EXPOSURE STUDIES/ Overdosage of hydralazine may produce hypotension, tachycardia, headache, and generalized skin flushing. Myocardial ischemia and cardiac arrhythmias may develop; profound shock can occur in severe overdosage.

/HUMAN EXPOSURE STUDIES/ ... This study was designed to establish the effects on lipid profiles of the angiotensin-converting enzyme inhibitors lisinopril and enalapril, alone and in combination with hydrochlorothiazide (HCTZ), the calcium-channel blocker nitrendipine, HCTZ, and hydralazine. After a two-week, single-blind, placebo phase, 77 patients with essential hypertension were given active agent as monotherapy in a double-blind fashion for 8-20 weeks. The dose of each agent was titrated to achieve diastolic blood pressure less than 90 mm Hg. At the end of placebo and treatment phases, plasma was analyzed for triglycerides, total cholesterol, and high-(HDL), and low-density lipoprotein (LDL) cholesterol. ... Total cholesterol decreased during therapy with hydralazine ... . LDL cholesterol was lowered during therapy with hydralazine ... . /Hydralazine did not/ significantly affect triglyceride concentrations. Thus, ... hydralazine lowers total and LDL cholesterol. ...

For more Human Toxicity Excerpts (Complete) data for HYDRALAZINE HYDROCHLORIDE (6 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Hydralazine hydrochloride

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Hydralazine was administered in drinking water as a 0.0312% solution to randomly bred Swiss mice for life beginning at 5 weeks of age. The treatments gave rise to statistically significant incidences of lung tumors: 55% in females and 43% in males. A decreased copper concentration and superoxide dismutase activity in the lung of mice were observed.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ An aqueous solution of 0.125% hydralazine hydrochloride (93% pure) was given continuously as drinking water for life to 50 male and 50 female random-bred Swiss mice, from 6 wks of age. The average daily intake of hydralazine hydrochloride was 7.4 mg for males and 5.4 mg for females. A control group consisted of 50 females and 50 males. Whenever a treated mouse died, a corresponding untreated control mouse was killed on the same day. Of the treated females, 30 (60%) developed 81 lung tumors; 19 mice had 40 adenomas, 2 had 2 adenocarcinomas, and 9 had 28 adenomas plus 11 adenocarcinomas. Their average age at death was 78 weeks; the first tumor was found at the 49th week and the last at the 98th week. In untreated females,18 (36%) developed 20 lung tumors; 15 mice had 17 adenomas, and 3 mice had 3 adenocarcinomas. Their average age at death was 78 wks; the first tumor was found at the 55th wk and the last at the 92nd wk. The increased incidence of lung tumors in females was statistically significant (P<0.014). In treated males, 23 (46%) developed 58 lung neoplasms; 14 mice had 21 adenomas; 1 mouse had an adenocarcinoma; and 8 had 24 adenomas plus 12 adenocarcinomas. Their average age at death was 79 wks; the first tumor was found at the 60th wk and the last at the 96th wk of age. In untreated males,13 (26%) developed 16 lung tumors; 9 mice had 9 adenomas; 4 had 4 adenocarcinomas; and 1 had 1 adenoma plus 2 adenocarcinomas. Their average age at death was 75 wks; the first tumor was found at the 54th wk and the last at the 95th wk of age (P<0.032). (Attention is drawn to the fact that the unusual design of the experiment, whereby a control mouse was killed each time a treated mouse died, was not followed by an appropriate analysis of the results. The fact that the purity of the compound (93%) was lower than USP standards (98%) was also noted.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Lupus erythematosus cells were found in the blood of 7 out of 8 dogs administered hydralazine hydrochloride at daily doses of 200 mg/dog for 2-8 months. The kidneys showed changes consistent with those found in disseminated lupus erythematosus. In other studies in dogs, daily doses of 20 mg/kg bw hydralazine (unspecified) daily for 2-12.5 months produced anaemia, which the authors said was probably hemolytic; no lupus erythematosus cells were found. Daily doses of 50-200 mg/dog for 29 weeks caused multifocal hepatic necrosis but no symptoms that showed a clear relationship with disseminated lupus erythematosus. The presence of antinuclear antibodies, an indicator of disseminated lupus erythematosus, was not detected in rats given 60 mg/kg bw hydralazine hydrochloride daily for 6 months. Antinuclear antibodies were detected in 30% of guinea-pigs after daily administration of 100 mg/animal of dihydralazine sulfate, a hydralazine derivative, for 7 months.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Animal studies indicate that hydralazine is teratogenic in mice at 20 to 30 times the maximum daily human dose of 200 to 300 mg and possible in rabits at 10 to 15 times the maximum daily human dose, but that it is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformation of facial and cranial bones.

/GENOTOXICITY/ Hydralazine was shown to be mutagenic in bacterial systems (gene mutation and DNA repair ) and in one of two rat and one rabbit hepatocyte in vitro DNA repair studies. Additional in vitro and in vivo studies using lymphoma cells, germinal cells, fibroblasts from mice, bone marrow cells from Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic potential for hydralazine.

Decontamination: Prehospital: Administer activated charcoal if available. Do not induce vomiting, because of the risk of hypotension and syncope. Hospital: Administer activated charcoal. Gastric emptying is not necessary if activated charcoal can be given promptly. /Vasodilators/

If the patient lives for 24 hr after a severe hypotensive reaction survival is likely. Complete recovery from rheumatoid reactions has always occurred.

A. Acute poisoning: 1. Emergency measures-establish airway and maintain respiration. Cautious reduction of dosage is indicated if severe hypotensive reactions. ...Treat hypotension with fluids. Vasopressors are hazardous.

Emergency and supportive measures: Maintain an open airway and assist ventilation of necessary. Hypotension usually responds to supine positioning and intravenous crystalloid fluids. Occasionally, pressor therapy is needed. /Vasodilators/

LD50 Rat oral 187 mg/kg (male)

LD50 Rat oral 173 mg/kg (female)

LD 50 Rat ip 35 mg/kg

LD50 Mouse (male) oral 260 mg/kg

LD50 Mouse (female) oral 210 mg/kg

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl hydralazine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Hydralazine causes direct relaxation of arteriolar smooth muscle. The molecular mechanism of this effect is not known. It is not a dilator of capacitance vessels (e.g., the epicardial coronary arteries) and does not relax venous smooth muscle. Hydralazine-induced vasodilatation is associated with powerful stimulation of the sympathetic nervous system, which results in increased heart rate and contractility, increased plasma renin activity, and fluid retention; all of these effects counteract the antihypertensive effect of hydralazine. Although most of the sympathetic activity is due to a baroreceptor-mediated reflex, hydralazine may stimulate the release of norepinephrine from sympathetic nerve terminals and augment myocardial contractility directly.

Compound /3-methyltriazolo(5,1-b)phthalazine/ is one of the major metabolites of hydralazine in human subjects.

Hydralazine is N-acetylated in the bowel and/or the liver. The rate of acetylation is genetically determined; about half of the people in the United States acetylate rapidly and half do so slowly.

Since the systemic clearance exceeds hepatic blood flow, extrahepatic metabolism must occur. ... Hydralazine rapidly combines with circulating alpha-keto acids to form hydrazones, and the major metabolite recovered from the plasma is hydralazine pyruvic acid hydrazone.

... Pharmacokinetic data indicate hydralazine ... has an extensive and complex metabolism depending on acetylator status: slow acetylators undergo primary oxidative metabolism, while rapid acetylators are acetylated. ...

HYDRALAZINE HYDROCHLORIDE

Arteriolar Vasodilator [EPC]; Arteriolar Vasodilation [PE]

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Drugs used to cause dilation of the blood vessels.

Hydralazine is well absorbed through the GI tract, but the systemic bioavailability is low (16% in fast acetylators and 35% in slow acetylators).

The peak concentration of hydralazine in plasma and the peak hypotensive effect of the drug occur within 30 to 120 minutes of ingestion. Although its half-life in plasma is about an hour, the duration of the hypotensive effect of hydralazine can last as long as 12 hours. There is no clear explanation for this discrepancy.

MEDICATION

MEDICATION (VET)

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

CONDENSATION OF 1-CHLOROPHTHALAZINE AND HYDRAZINE HYDRATE IN AN ORGANIC SOLVENT

PREPD BY THE ACTION OF HYDRAZINE HYDRATE ON 1-CHLORO- OR 1-PHENOXYPHTHALAZINE: HARTMANN, DRUEY, US PATENT 2484029 (1949 TO CIBA) ... . /HYDRALAZINE/

1-HYDRAZINOPHTHALAZINE

1 (2H)-PHTHALAZINONE HYDRAZONE

PRAPARAT 5968

C 5968

For more Formulations/Preparations (Complete) data for HYDRALAZINE HYDROCHLORIDE (7 total), please visit the HSDB record page.

Phthalazine, 1-hydrazinyl-, hydrochloride (1:1): ACTIVE

There are no technical products or pharmaceutical preparations containing the free base. It is used in the preparation of the hydrochloride salt.