Sulmetin Papaverina Tablets

Magnesium Gluconate:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Sulmetin Papaverina Tablets (Magnesium Gluconate) reviews

Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate Injection, USP is a sterile solution of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.

Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate, USP heptahydrate is chemically designated MgSO₄ - 7H₂O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

CLINICAL PHARMACOLOGY

Sulmetin Papaverina Tablets (Magnesium Gluconate) (Mg⁺⁺) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for Sulmetin Papaverina Tablets (Magnesium Gluconate) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.

Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of Sulmetin Papaverina Tablets (Magnesium Gluconate). While there are large stores of Sulmetin Papaverina Tablets (Magnesium Gluconate) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Sulmetin Papaverina Tablets (Magnesium Gluconate) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Sulmetin Papaverina Tablets (Magnesium Gluconate) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Sulmetin Papaverina Tablets (Magnesium Gluconate) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma Sulmetin Papaverina Tablets (Magnesium Gluconate) levels range from 1.5 to 2.5 mEq/liter.

As plasma Sulmetin Papaverina Tablets (Magnesium Gluconate) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of Sulmetin Papaverina Tablets (Magnesium Gluconate). Serum Sulmetin Papaverina Tablets (Magnesium Gluconate) concentrations in excess of 12 mEq/L may be fatal.

Sulmetin Papaverina Tablets (Magnesium Gluconate) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of Sulmetin Papaverina Tablets (Magnesium Gluconate) poisoning are antagonized to some extent by intravenous administration of calcium.

Pharmacokinetics

With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Sulmetin Papaverina Tablets (Magnesium Gluconate) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate Injection, USP is suitable for replacement therapy in Sulmetin Papaverina Tablets (Magnesium Gluconate) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Sulmetin Papaverina Tablets (Magnesium Gluconate) (Mg⁺⁺) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca⁺⁺) level is normal (4.3 to 5.3 mEq/liter) or elevated.

In total parenteral nutrition (TPN), Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.

WARNINGS

FETAL HARM: Continuous administration of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate should be used during pregnancy only if clearly needed. If Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate beyond 5 to 7 days may cause fetal abnormalities.

ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Parenteral use in the presence of renal insufficiency may lead to Sulmetin Papaverina Tablets (Magnesium Gluconate) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with Sulmetin Papaverina Tablets (Magnesium Gluconate), their dosage should be adjusted with caution because of additive CNS depressant effects of Sulmetin Papaverina Tablets (Magnesium Gluconate).

Because Sulmetin Papaverina Tablets (Magnesium Gluconate) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum Sulmetin Papaverina Tablets (Magnesium Gluconate) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional Sulmetin Papaverina Tablets (Magnesium Gluconate) should be given until they return. Serum Sulmetin Papaverina Tablets (Magnesium Gluconate) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when Sulmetin Papaverina Tablets (Magnesium Gluconate) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of Sulmetin Papaverina Tablets (Magnesium Gluconate) intoxication in eclampsia.

50% Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Sulmetin Papaverina Tablets (Magnesium Gluconate) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with Sulmetin Papaverina Tablets (Magnesium Gluconate), their dosage should be adjusted with caution because of additive CNS depressant effects of Sulmetin Papaverina Tablets (Magnesium Gluconate). CNS depression and peripheral transmission defects produced by Sulmetin Papaverina Tablets (Magnesium Gluconate) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat Sulmetin Papaverina Tablets (Magnesium Gluconate) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate for more than 5 to 7 days.^1-10 Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.

Nonteratogenic Effects

When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of Sulmetin Papaverina Tablets (Magnesium Gluconate) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since Sulmetin Papaverina Tablets (Magnesium Gluconate) is distributed into milk during parenteral Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum Sulmetin Papaverina Tablets (Magnesium Gluconate) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Sulmetin Papaverina Tablets (Magnesium Gluconate) usually are the result of Sulmetin Papaverina Tablets (Magnesium Gluconate) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Sulmetin Papaverina Tablets (Magnesium Gluconate) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of Sulmetin Papaverina Tablets (Magnesium Gluconate) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Sulmetin Papaverina Tablets (Magnesium Gluconate).

For Treatment of Overdose

Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.

Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

DOSAGE AND ADMINISTRATION

Dosage of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.

In Sulmetin Papaverina Tablets (Magnesium Gluconate) Deficiency

In the treatment of mild Sulmetin Papaverina Tablets (Magnesium Gluconate) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Sulmetin Papaverina Tablets (Magnesium Gluconate) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Sulmetin Papaverina Tablets (Magnesium Gluconate) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.

In Hyperalimentation

In total parenteral nutrition, maintenance requirements for Sulmetin Papaverina Tablets (Magnesium Gluconate) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.

In Pre-eclampsia or Eclampsia

In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum Sulmetin Papaverina Tablets (Magnesium Gluconate) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate is 20 grams/48 hours and frequent serum Sulmetin Papaverina Tablets (Magnesium Gluconate) concentrations must be obtained. Continuous use of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate is 1 gram to 2 grams given intravenously.

For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.

In paroxysmal atrial tachycardia, Sulmetin Papaverina Tablets (Magnesium Gluconate) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.

For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.

Incompatibilities

Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.

It has been reported that Sulmetin Papaverina Tablets (Magnesium Gluconate) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate Injection, USP is supplied in single-dose containers as follows:

Do not administer unless solution is clear and container is undamaged. Discard unused portion.

Store at 20 to 25°C (68 to 77°F).

REFERENCES

• Yokoyama K, Takahashi N, Yada Y. Prolonged maternal Sulmetin Papaverina Tablets (Magnesium Gluconate) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
• Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal Sulmetin Papaverina Tablets (Magnesium Gluconate) toxicity. J. Perinatol. 2006; 26(6):371-4.
• Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
• Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Sulmetin Papaverina Tablets (Magnesium Gluconate) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
• Matsuda Y, Maeda Y, Ito M, et al. Effect of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
• Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
• Santi MD, Henry GW, Douglas GL. Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
• Holcomb WL, Shackelford GD, Petrie RH. Sulmetin Papaverina Tablets (Magnesium Gluconate) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
• Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
• Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
• McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
• Riaz M, Porat R, Brodsky NL, et al. The effects of maternal Sulmetin Papaverina Tablets (Magnesium Gluconate) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Sulmetin Papaverina Tablets (Magnesium Gluconate) Sulfate Injection, USP

5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)

MUST BE DILUTED FOR INTRAVENOUS USE.

For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Papaverine Hydrochloride:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Sulmetin Papaverina Tablets (Papaverine Hydrochloride) reviews

Rx Only

This product is to be used by or under the direction of a physician.

Each vial contains a sufficient amount to permit withdrawal and administration of the volume specified on the label.

DESCRIPTION

Sulmetin Papaverina Tablets (Papaverine Hydrochloride), USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine.

Sulmetin Papaverina Tablets (Papaverine Hydrochloride), USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C₂₀H₂₁NO₄-HCI. The molecular weight is 375.85. The structural formula is as shown.

Sulmetin Papaverina Tablets (Papaverine Hydrochloride) occurs as white crystals or white crystalline powder. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether.

Sulmetin Papaverina Tablets (Papaverine Hydrochloride) Injection, USP, is a clear, colorless to pale-yellow solution.

Sulmetin Papaverina Tablets (Papaverine Hydrochloride), for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. The 10 mL vials also contain chlorobutanol 0.5% as a preservative. pH may be adjusted with sodium citrate and/or citric acid.

Adobe Systems

CLINICAL PHARMACOLOGY

The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Sulmetin Papaverina Tablets (Papaverine Hydrochloride) apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.

The main actions of papaverine are exerted on cardiac and smooth muscle. Papaverine relaxes various smooth muscles, especially those of larger arteries; this relaxation may be prominent if spasm exists. The antispasmodic effect is a direct one and unrelated to muscle innervation, and the muscle still responds to drugs and other stimuli causing contraction. Papaverine has minimal actions on the central nervous system, although very large doses tend to produce some sedation and sleepiness in some patients. In certain circumstances, mild respiratory stimulation can be observed, but this is therapeutically inconsequential. Papaverine stimulates respiration by acting on carotid and aortic body chemoreceptors.

Papaverine relaxes the smooth musculature of the larger blood vessels, including the coronary, cerebral, peripheral, and pulmonary arteries. This action is particularly evident when such vessels are in spasm, induced reflexly or by drugs, and it provides the basis for the clinical use of papaverine in peripheral or pulmonary arterial embolism.

Experimentally in dogs, the alkaloid has been shown to cause fairly marked and long-lasting coronary vasodilatation and an increase in coronary blood flow. However, it also appears to have a direct inotropic effect and, when increased mechanical activity coincides with decreased systemic pressure, increases in coronary blood flow may not be sufficient to prevent brief periods of hypoxic myocardial depression.

Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. It is metabolized in the liver. About 90% of the drug is bound to plasma protein. Although estimates of its biologic half-life vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.

INDICATIONS AND USAGE

Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal colic.

CONTRAINDICATIONS

Intravenous injection of papaverine is contraindicated in the presence of complete atrioventricular heart block. When conduction is depressed, the drug may produce transient ectopic rhythms of ventricular origin, either premature beats or paroxysmal tachycardia.

Sulmetin Papaverina Tablets (Papaverine Hydrochloride) is not indicated for the treatment of impotence by intracorporeal injection. The intracorporeal injection of Sulmetin Papaverina Tablets (Papaverine Hydrochloride) has been reported to have resulted in persistent priapism requiring medical and surgical intervention.

PRECAUTIONS

General

Sulmetin Papaverina Tablets Injection, USP, should not be added to Lactated Ringer’s Injection, because precipitation would result.

Sulmetin Papaverina Tablets (Papaverine Hydrochloride) should be used with caution in patients with glaucoma. The medication should be discontinued if hepatic hypersensitivity with gastrointestinal symptoms, jaundice, or eosinophilia becomes evident or if liver function test values become altered.

Pregnancy

Pregnancy Category C - No teratogenic effects were observed in rats when Sulmetin Papaverina Tablets (Papaverine Hydrochloride) was administered subcutaneously as a single agent. It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sulmetin Papaverina Tablets (Papaverine Hydrochloride) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sulmetin Papaverina Tablets is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children have not been established.

ADVERSE REACTIONS

The following side effects have been reported: general discomfort, nausea, abdominal discomfort, anorexia, constipation or diarrhea, skin rash, malaise, vertigo, headache, intensive flushing of the face, perspiration, increase in the depth of respiration, increase in heart rate, a slight rise in blood pressure, and excessive sedation.

Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.

DRUG ABUSE AND DEPENDENCE

Drug dependence resulting from the abuse of many of the selective depressants, including Sulmetin Papaverina Tablets (Papaverine Hydrochloride), has been reported.

OVERDOSAGE

Signs and Symptoms –

The symptoms of toxicity from Sulmetin Papaverina Tablets often result from vasomotor instability and include nausea, vomiting, weakness, central nervous system depression, nystagmus, diplopia, diaphoresis, flushing, dizziness, and sinus tachycardia. In large overdoses, papaverine is a potent inhibitor of cellular respiration and a weak calcium antagonist. Following an oral overdose of 15 g, metabolic acidosis with hyperventilation, hyperglycemia, and hypokalemia have been reported. No information on toxic serum concentrations is available.

Following intravenous overdosing in animals, seizures, tachyarrhythmias, and ventricular fibrillation have been reported. The oral median lethal dose in rats is 360 mg/kg.

Treatment –

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physician’s Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor vital signs, blood gases, blood chemistry values, and other variables.

If convulsions occur, consider diazepam, phenytoin, or phenobarbital. If the seizures are refractory, general anesthesia with thiopental or halothane and paralysis with a neuromuscular blocking agent may be necessary.

For hypotension, consider intravenous fluids, elevation of the legs, and an inotropic vasopressor, such as dopamine or norepinephrine (levarterenol). Theoretically, calcium gluconate may be helpful in treating some of the toxic cardiovascular effects of papaverine; monitor the ECG and plasma calcium concentrations.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of Sulmetin Papaverina Tablets (Papaverine Hydrochloride).

DOSAGE AND ADMINISTRATION

Sulmetin Papaverina Tablets (Papaverine Hydrochloride) may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.

Parenteral administration of Sulmetin Papaverina Tablets (Papaverine Hydrochloride) in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.

HOW SUPPLIED

Sulmetin Papaverina Tablets (Papaverine Hydrochloride) Injection, USP, 30 mg/mL

0517-4002-25 2 mL Vial packaged in boxes of 25

0517-4010-01 10 mL Multiple Dose Vial* packaged individually

*The 10 mL Multiple Dose Vial contains chlorobutanol 0.5% as a preservative.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

PROTECT FROM LIGHT. RETAIN IN CARTON UNTIL TIME OF USE.

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

IN4002

Rev. 1/09