Hydralazine Hydrochloride

1 INDICATIONS AND USAGE Essential hypertension, alone or as an adjunct.

DOSAGE AND ADMINISTRATION Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10 mg four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the balance of the first week. For the second and subsequent weeks, increase dosage to 50 mg four times daily. For maintenance, adjust dosage to the lowest effective levels. The incidence of toxic reactions, particularly the L.E. cell syndrome, is high in the group of patients receiving large doses of hydrALAZINE hydrochloride tablets, USP. In a few resistant patients, up to 300 mg of hydrALAZINE hydrochloride tablets, USP daily may be required for a significant antihypertensive effect. In such cases, a lower dosage of hydrALAZINE hydrochloride tablets, USP combined with a thiazide and/or reserpine or a beta blocker may be considered. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug.

CONTRAINDICATIONS: Hypersensitivity to hydrALAZINE; coronary artery disease; mitral valvular rheumatic heart disease.

ADVERSE REACTIONS Adverse reactions with hydrALAZINE are usually reversible when dosage is reduced. However, in some cases it may be necessary to discontinue the drug. The following adverse reactions have been observed, but there has not been enough systematic collection of data to support an estimate of their frequency. Common headache, anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, angina pectoris. Less Frequent Digestive constipation, paralytic ileus. Cardiovascular hypotension, paradoxical pressor response, edema. Respiratory dyspnea. Neurologic peripheral neuritis, evidenced by paresthesia, numbness, and tingling; dizziness; tremors; muscle cramps; psychotic reactions characterized by depression, disorientation, or anxiety. Genitourinary difficulty in urination. Hematologic blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, purpura; lymphadenopathy; splenomegaly. Hypersensitive Reactions rash, urticaria, pruritus, fever, chills, arthralgia, eosinophilia, and rarely, hepatitis. Other nasal congestion, flushing, lacrimation, conjunctivitis. Call your doctor for medical advice about side effects. You may report side effects to strides Pharma Inc. at 1-877-244-9825 or go to www.stridesshasun.com

Drug/Drug Interactions : MAO inhibitors should be used with caution in patients receiving hydralazine. When other potent parenteral antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure. Profound hypotensive episodes may occur when diazoxide injection and hydralazine are used concomitantly. Drug/Food Interactions: Administration of hydralazine with food results in higher plasma levels. Carcinogenesis, Mutagenesis, Impairment of Fertility : In a lifetime study in Swiss albino mice, there was a statistically significant increase in the incidence of lung tumors (adenomas and adenocarcinomas) of both male and female mice given hydralazine continuously in their drinking water at a dosage of about 250 mg/kg per day (about 80 times the maximum recommended human dose). In a 2-year carcinogenicity study of rats given hydralazine by gavage at dose levels of 15, 30, and 60 mg/kg/day (approximately 5 to 20 times the recommended human daily dosage), microscopic examination of the liver revealed a small, but statistically significant, increase in benign neoplastic nodules in male and female rats from the high-dose group and in female rats from the intermediate-dose group. Benign interstitial cell tumors of the testes were also significantly increased in male rats from the high-dose group. The tumors observed are common in aged rats and a significantly increased incidence was not observed until 18 months of treatment. Hydralazine was shown to be mutagenic in bacterial systems (Gene Mutation and DNA Repair) and in one of two rats and one rabbit hepatocyte in vitro DNA repair studies. Additional in vivo and in vitro studies using lymphoma cells, germinal cells, and fibroblasts from mice, bone marrow cells from Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic potential for hydralazine. The extent to which these findings indicate a risk to man is uncertain. While long-term clinical observation has not suggested that human cancer is associated with hydralazine use, epidemiologic studies have so far been insufficient to arrive at any conclusions. Pregnancy: Pregnancy Category C Teratogenic Effects: 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 possibly in rabbits at 10 to 15 times the maximum daily human dose, but that is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of facial and cranial bones. There are no adequate and well-controlled studies in pregnant women. Although clinical experience does not include any positive evidence of adverse effects on the human fetus, hydralazine should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus. Nursing Mothers: Hydralazine has been shown to be excreted in breast milk. Pediatric Use: Safety and effectiveness in pediatric patients have not been established in controlled clinical trials, although there is experience with the use of hydralazine in pediatric patients. The usual recommended oral starting dosage is 0.75 mg/kg of body weight daily in four divided doses. Dosage may be increased gradually over the next 3 to 4 weeks to a maximum of 7.5 mg/kg or 200 mg daily.

DESCRIPTION: HydrALAZINE Hydrochloride Tablets, USP, is an antihypertensive, for oral administration. Its chemical name is 1-hydrazinophthalazine monohydrochloride, and its structural formula is: C 8 H 8 N 4 • HCl HydrALAZINE Hydrochloride, USP is a white to off-white, odorless crystalline powder. It is soluble in water, slightly soluble in alcohol, and very slightly soluble in ether. It melts at about 275°C, with decomposition, and has a molecular weight of 196.64. Each tablet for oral administration contains 10 mg, 25 mg, 50 mg or 100 mg hydrALAZINE Hydrochloride, USP. 25 mg, 50 mg or 100 mg tablets also contain Anhydrous Lactose, Microcrystalline Cellulose, Sodium Starch Glycolate, Stearic Acid and Sunset Yellow Lake and 10 mg tablets contain Magnesium Stearate, Mannitol, Microcrystalline Cellulose, Sodium Starch Glycolate, and Sunset Yellow Lake. structure

OVERDOSAGE: Acute Toxicity: No deaths due to acute poisoning have been reported. Highest known dose survived: adults, 10 g orally. Oral LD 50 in rats: 173 and 187 mg/kg. Signs and Symptoms: Signs and symptoms of overdosage include hypotension, tachycardia, headache, and generalized skin flushing. Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia, and profound shock. Treatment: There is no specific antidote. The gastric contents should be evacuated, taking adequate precautions against aspiration and for protection of the airway. An activated charcoal slurry may be instilled if conditions permit. These manipulations may have to be omitted or carried out after cardiovascular status has been stabilized, since they might precipitate cardiac arrhythmias or increase the depth of shock. Support of the cardiovascular system is of primary importance. Shock should be treated with plasma expanders. If possible, vasopressors should not be given, but if a vasopressor is required, care should be taken not to precipitate or aggravate cardiac arrhythmia. Tachycardia responds to beta blockers. Digitalization may be necessary, and renal function should be monitored and supported as required. No experience has been reported with extracorporeal or peritoneal dialysis. DOSAGE AND ADMINISTRATION: Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10 mg four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the balance of the first week. For the second and subsequent weeks, increase dosage to 50 mg four times daily. For maintenance, adjust dosage to the lowest effective levels. The incidence of toxic reactions, particularly the L.E. cell syndrome, is high in the group of patients receiving large doses of hydrALAZINE. In a few resistant patients, up to 300 mg of hydrALAZINE daily may be required for a significant antihypertensive effect. In such cases, a lower dosage of hydrALAZINE combined with a thiazide and/or reserpine or a beta blocker may be considered. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug. HOW SUPPLIED: HydrALAZINE Hydrochloride Tablets, USP: 10 mg - Orange, round, unscored tablets debossed with ‘H’ on one side and ‘38’ on the other side. 25 mg - Orange, round, unscored tablets debossed with ‘H’ on one side and ‘39’ on the other side. 50 mg - Orange, round, unscored tablets debossed with ‘H’ on one side and ‘40’ on the other side. 100 mg - Orange, round, unscored tablets debossed with ‘H’ on one side and ‘41’ on the other side in blistercards of 30 (NDC code: 0615-7973-39) and blistercards of 15 (NDC code: 0615-7973-05). Dispense in a tight, light-resistant container as defined in the USP. Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 By: HeteroTM Hetero Labs Limited Jeedimetla, Hyderabad- 500 055, India 2038197

HOW SUPPLIED HydrALAZINE Hydrochloride Tablets, USP are available as: 10 mg – Round, peach core tablet, debossed EP on one side and 101 on the reverse side. Cartons of 100 tablets (10 tablets each blister pack x 10), NDC 0904-7447-61 25 mg – Round, peach, core tablet, debossed EP over 102 on one side and plain on the reverse side. Cartons of 100 tablets (10 tablets each blister pack x 10), NDC 0904-7448-61 50 mg – Round, peach, core tablet, debossed EP over 103 on one side and plain on the reverse side. Cartons of 100 tablets (10 tablets each blister pack x 10), NDC 0904-7449-61 100 mg – Round, Peach, core tablet, debossed EP over 104 on one side and plain on the reverse side. Cartons of 100 tablets (10 tablets each blister pack x 10), NDC 0904-7450-61 WARNING: These Unit Dose packages are not child resistant and are Intended for Institutional Use Only. Keep this and all drugs out of the reach of children. Dispense in a tight, light-resistant container as defined in the USP. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Manufactured by: Stallion Laboratories Private Limited Gallops Industrial Park-II, Ahmedabad-382110, Gujarat, India Distributed by: Avet Pharmaceuticals Inc. East Brunswick, NJ 08816 1-866-901-DRUG (3784) Packaged and Distributed by: MAJOR® PHARMACEUTICALS Indianapolis, IN 46268 USA Refer to package label for Distributor's NDC Number Revised: 06/2025 logo