Weight Loss

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Several drugs, including para-aminosalicylic acid, have been reported to reduce the absorption of methylcobalamin, vitamin B12. Monitor for the desired therapeutic response to vitamin B12.

The heavy consumption of ethanol for greater than 2 weeks has been reported to reduce the absorption of Methylcobalamin, vitamin B12. Patients should be aware that heavy, chronic ethanol use may counteract the therapeutic effects of vitamin B12; such patients with regular and chronic ethanol consumption be monitored for the desired therapeutic response to vitamin B12.

Several drugs, including colchicine, have been reported to reduce the absorption of methylcobalamin, vitamin B12. Colchicine has been shown to induce reversible malabsorption of vitamin B12, apparently by altering the function of ileal mucosa. Although further study of these interactions is necessary, patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12.

In a study of 10 healthy male volunteers, omeprazole, in doses of 20 mg—40 mg per day, caused a significant decrease in the oral absorption of methylcobalamin, vitamin B12. Theoretically this interaction is possible with other proton pump inhibitors (PPIs), although specific clinical data are lacking. Patients receiving long-term therapy with omeprazole or other proton pump inhibitors (PPIs) should be monitored for signs of B12deficiency.

Chloramphenicol can antagonize the hematopoietic response to Methylcobalamin, vitamin B12 through interference with erythrocyte maturation. Chloramphenicol is known to cause bone marrow suppression, especially when serum concentrations exceed 25 mcg/ml. Chloramphenicol should be discontinued if anemia attributable to chloramphenicol is noted during periodic blood studies, which should be done approximately every 2 days during chloramphenicol receipt. Aplastic anemia and hypoplastic anemia are known to occur after chloramphenicol administration. Peripherally, pancytopenia is most often observed, but only 1—2 of the major cell types (erythrocytes, leukocytes, platelets) may be depressed in some cases.

Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. The interaction very rarely results in a pernicious anemia that appears reversible with discontinuation of metformin or with Methylcobalamin, vitamin B12 supplementation. Certain individuals may be predisposed to this interaction. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.

Medications know to cause bone marrow suppression (e.g., myelosuppressive antineoplastic agents) may result in a blunted or impeded response to methylcobalamin, vitamin B12 therapy. Antineoplastics that are antimetabolites for the vitamin may induce inadequate utilization of vitamin B12. However, cancer patients usually benefit from vitamin B12 supplementation. The use of methotrexate may additionally invalidate diagnostic assays for folic acid and vitamin B12; however, this is a diagnostic laboratory test interference and not a drug interaction.

The intranasal forms of methylcobalamin, vitamin B12, should be administered at least 1 hour before or 1 hour after ingestion of hot food or liquids. Hot foods may cause nasal secretions and a resulting loss of medication or medication efficacy. Interactions between foods and oral or injectable forms of methylcobalamin are not expected.

Depressed levels of methylcobalamin, vitamin B12, and abnormal Schilling’s test have been reported in patients receiving octreotide.

The use of antiinfective agents or pyrimethamine may invalidate diagnostic assays for folic acid and vitamin B12; however, these are diagnostic laboratory test interferences and not true drug interactions.

In most cases, methylcobalamin is nontoxic, even in large doses. Adverse reactions reported following methylcobalamin administration include headache, infection, nausea/vomiting, paresthesias, and rhinitis. Adverse reactions following intramuscular (IM) injection have included anxiety, mild transient diarrhea, ataxia, nervousness, pruritus, transitory exanthema, and a feeling of swelling of the entire body. Some patients have also experienced a hypersensitivity reaction following intramuscular injection that has resulted in anaphylactic shock and death. In cases of suspected cobalt hypersensitivity, an intradermal test dose should be administered.

During the initial treatment period with methylcobalamin, pulmonary edema and congestive heart failure have reportedly occurred early in treatment with parenteral methylcobalamin. This is believed to result from the increased blood volume induced by methylcobalamin. Peripheral vascular thrombosis has also occurred. In post-marketing experience, angioedema and angioedema-like reactions were reported with parenteral methylcobalamin.

Hypokalemia and thrombocytosis could occur upon conversion of severe megaloblastic anemia to normal erythropoiesis with methylcobalamin therapy. Therefore, monitoring of the platelet count and serum potassium concentrations are recommended during therapy. Polycythemia vera has also been reported with parenteral methylcobalamin.

Diarrhea and headache.

Call your health care provider immediately if you are experiencing any signs of an allergic reaction: skin rash, itching or hives, swelling of the face, lips, or tongue, blue tint to skin, chest tightness, pain, difficulty breathing, wheezing, dizziness, red, swollen painful area on the leg.

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Several drugs, including para-aminosalicylic acid, have been reported to reduce the absorption of methylcobalamin, vitamin B12. Monitor for the desired therapeutic response to vitamin B12.

The heavy consumption of ethanol for greater than 2 weeks has been reported to reduce the absorption of Methylcobalamin, vitamin B12. Patients should be aware that heavy, chronic ethanol use may counteract the therapeutic effects of vitamin B12; such patients with regular and chronic ethanol consumption be monitored for the desired therapeutic response to vitamin B12.

Several drugs, including colchicine, have been reported to reduce the absorption of methylcobalamin, vitamin B12. Colchicine has been shown to induce reversible malabsorption of vitamin B12, apparently by altering the function of ileal mucosa. Although further study of these interactions is necessary, patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12.

In a study of 10 healthy male volunteers, omeprazole, in doses of 20 mg—40 mg per day, caused a significant decrease in the oral absorption of methylcobalamin, vitamin B12. Theoretically this interaction is possible with other proton pump inhibitors (PPIs), although specific clinical data are lacking. Patients receiving long-term therapy with omeprazole or other proton pump inhibitors (PPIs) should be monitored for signs of B12deficiency.

Chloramphenicol can antagonize the hematopoietic response to Methylcobalamin, vitamin B12 through interference with erythrocyte maturation. Chloramphenicol is known to cause bone marrow suppression, especially when serum concentrations exceed 25 mcg/ml. Chloramphenicol should be discontinued if anemia attributable to chloramphenicol is noted during periodic blood studies, which should be done approximately every 2 days during chloramphenicol receipt. Aplastic anemia and hypoplastic anemia are known to occur after chloramphenicol administration. Peripherally, pancytopenia is most often observed, but only 1—2 of the major cell types (erythrocytes, leukocytes, platelets) may be depressed in some cases.

Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. The interaction very rarely results in a pernicious anemia that appears reversible with discontinuation of metformin or with Methylcobalamin, vitamin B12 supplementation. Certain individuals may be predisposed to this interaction. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.

Medications know to cause bone marrow suppression (e.g., myelosuppressive antineoplastic agents) may result in a blunted or impeded response to methylcobalamin, vitamin B12 therapy. Antineoplastics that are antimetabolites for the vitamin may induce inadequate utilization of vitamin B12. However, cancer patients usually benefit from vitamin B12 supplementation. The use of methotrexate may additionally invalidate diagnostic assays for folic acid and vitamin B12; however, this is a diagnostic laboratory test interference and not a drug interaction.

The intranasal forms of methylcobalamin, vitamin B12, should be administered at least 1 hour before or 1 hour after ingestion of hot food or liquids. Hot foods may cause nasal secretions and a resulting loss of medication or medication efficacy. Interactions between foods and oral or injectable forms of methylcobalamin are not expected.

Depressed levels of methylcobalamin, vitamin B12, and abnormal Schilling’s test have been reported in patients receiving octreotide.

The use of antiinfective agents or pyrimethamine may invalidate diagnostic assays for folic acid and vitamin B12; however, these are diagnostic laboratory test interferences and not true drug interactions.

Methylcobalamin is distributed into breast milk in amounts similar to those in maternal plasma, and distribution in breast milk allows for adequate intakes of methylcobalamin by breast-feeding infants. Adequate maternal intake is important for both the mother and infant during nursing, and maternal requirements for vitamin B12 increase during lactation. According to the manufacturer, the usual daily recommended amounts of methylcobalamin, vitamin B12 for lactating women should be taken maternally during breast-feeding (see Dosage). The American Academy of Pediatrics considers vitamin B12 to be compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Parenteral methylcobalamin is classified as pregnancy category C. Adequate studies in humans have not been conducted; however, no maternal or fetal complications have been associated with doses that are recommended during pregnancy, and appropriate treatment should not be withheld from pregnant women with vitamin B12 responsive anemias. Conversely, pernicious anemia resulting from vitamin B12 deficiency may cause infertility or poor pregnancy outcomes. Vitamin B12 deficiency has occurred in breast-fed infants of vegetarian mothers whose diets contain no animal products (e.g., eggs, dairy), even though the mothers had no symptoms of deficiency at the time. Maternal requirements for vitamin B12 increase during pregnancy. The usual daily recommended amounts of methylcobalamin, vitamin B12 either through dietary intake or supplementation should be taken during pregnancy (see Dosage).

Who should not take this medication? Patients with early hereditary optic nerve atrophy, cyanocobalmin hypersensitivity, and those who are pregnant. Your health care provider needs to know if you have any of these conditions: kidney disease; Leber’s disease; megaloblastic anemia; an unusual or allergic reaction to methylcobalamin, cobalt, other medicines, foods, dyes, or preservatives; pregnant or trying to get pregnant; breast-feeding.

Methylcobalamin is contraindicated in patients with methylcobalamin hypersensitivity or hypersensitivity to any of the medication components. Methylcobalamin is also contraindicated in patients with cobalt hypersensitivity because methylcobalamin contains cobalt. In the case of suspected cobalt hypersensitivity, an intradermal test dose should be administered because anaphylactic shock and death have followed parenteral administration of methylcobalamin.

Methylcobalamin should not be used in patients with early hereditary optic nerve atrophy (Leber’s disease). Optic nerve atrophy can worsen in patients whose methylcobalamin levels are already elevated. Hydroxocobalamin is the preferred agent in this patient population (see separate monograph in Less Common Drugs).

Most formulations of methylcobalamin injection contain benzyl alcohol as a preservative. Benzyl alcohol may cause allergic reactions. Methylcobalamin injections should be used cautiously in those patients with benzyl alcohol hypersensitivity. Methylcobalamin, vitamin B12 preparations containing benzyl alcohol should be avoided in premature neonates because benzyl alcohol has been associated with ‘gasping syndrome,’ a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction.

Vitamin B12 deficiency can suppress the symptoms of polycythemia vera. Treatment with methylcobalamin or hydroxocobalamin may unmask this condition.

Folic Acid, vitamin B9 is not a substitute for methylcobalamin, vitamin B12 deficiency, although it may improve vitamin B12 megaloblastic anemia. However, exclusive use of folic acid in treating vitamin B12 deficient megaloblastic anemia could result in progressive and irreversible neurologic damage. Before receiving folic acid or methylcobalamin, patients should be assessed for deficiency and appropriate therapy started concurrently. The intranasal formulations are not approved to treat acute B12 deficiency; all hematologic parameters should be normal before beginning the methylcobalamin intranasal formulations. Concurrent iron-deficiency anemia and folic acid deficiency may result in a blunted or impeded response to methylcobalamin therapy.

Certain conditions may blunt or impede therapeutic response to methylcobalamin therapy. These include serious infection, uremia or renal failure, drugs with bone marrow suppression properties (e.g., chloramphenicol), or concurrent undiagnosed folic acid or iron deficiency anemia. The mechanism appears to be interference with erythropoiesis. Patients with vitamin B12 deficiency and concurrent renal or hepatic disease may require increased doses or more frequent administration of methylcobalamin.

Clinical reports have not identified differences in responses between elderly and younger patients. Generally, dose selection for elderly patients should be done with caution. Elderly patients tend to have a greater frequency of decreased hepatic, renal, or cardiac function, and also have concomitant disease or receiving other drug therapy. Start with doses at the lower end of the dosing range.

Methylcobalamin is administered intranasally, orally, and parenterally, while hydroxocobalamin is administered only parenterally. Once absorbed, vitamin B12 is highly bound to transcobalamin II, a specific B-globulin carrier protein and is distributed and stored primarily in the liver as coenzyme B12. The bone marrow also stores a significant amount of the absorbed vitamin B12. This vitamin crosses the placenta and is distributed into breast milk. Enterohepatic recirculation conserves systemic stores. The half-life is about 6 days (400 days in the liver). Elimination is primarily through the bile; however, excess methylcobalamin is excreted unchanged in the urine.

Intramuscular Route Specific Pharmacokinetics: Bioavailability of the nasal gel and spray forms relative to an IM injection are about 9% and 6%, respectively. Because the intranasal forms have lower absorption than the IM dosage form, intranasal B12 forms are administered once weekly. After 1 month of treatment in pernicious anemia patients, the once weekly dosing of 500 mcg B12 intranasal gel resulted in a statistically significant increase in B12 levels when compared to a once monthly 100 mcg IM dose.

Route-Specific Pharmacokinetics:

Intravenous Route: Peak plasma levels of cyanocobalamin are attained within 1 hour for parenteral doses.

Vitamin B12 is used in the body in two forms, methylcobalamin and 5-deoxyadenosyl cobalamin. The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine which is, in turn, required for DNA methylation. The other form, 5-deoxyadenosylcobalamin, is a cofactor needed by the enzyme that converts L-methylmalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of energy from proteins and fats. Furthermore, succinyl CoA is necessary for the production of hemoglobin, the substance that carries oxygen in red blood cells.

Vitamin B12, or methylcobalamin, is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cells characterized by rapid division (epithelial cells, bone marrow, myeloid cells) appear to have the greatest requirement for methylcobalamin. Vitamin B12 can be converted to coenzyme B12 in tissues; in this form it is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine (a reaction which also requires folate). In the absence of coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyl tetrahydrofolate, resulting in functional folate deficiency. Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems. Through these reactions, vitamin B12 is associated with fat and carbohydrate metabolism and protein synthesis. Vitamin B12 deficiency results in megaloblastic anemia, GI lesions, and neurologic damage (which begins with an inability to produce myelin and is followed by gradual degeneration of the axon and nerve head). Vitamin B12 requires an intrinsic factor-mediated active transport for absorption, therefore, lack of or inhibition of intrinsic factor results in pernicious anemia.

Methylcobalamin, or vitamin B12, is a B-vitamin. It is found in a variety of foods such as fish, shellfish, meats, and dairy products. Although methylcobalamin and vitamin B12 are terms used interchangeably, vitamin B12 is also available as hydroxocobalamin, a less commonly prescribed drug product, and methylcobalamin. Methylcobalamin is used to treat pernicious anemia and vitamin B12 deficiency, as well as to determine vitamin B12 absorption in the Schilling test. Vitamin B12 is an essential vitamin found in the foods such as meat, eggs, and dairy products. Deficiency in healthy individuals is rare; the elderly, strict vegetarians (i.e., vegan), and patients with malabsorption problems are more likely to become deficient. If vitamin B12 deficiency is not treated with a vitamin B12 supplement, then anemia, intestinal problems, and irreversible nerve damage may occur.

The most chemically complex of all the vitamins, methylcobalamin is a water-soluble, organometallic compound with a trivalent cobalt ion bound inside a corrin ring which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Methylcobalamin cannot be made by plants or by animals; the only type of organisms that have the enzymes required for the synthesis of methylcobalamin are bacteria and archaea. Higher plants do not concentrate methylcobalamin from the soil, making them a poor source of the substance as compared with animal tissues.

10,000 mcg Lyophilized Vial

50,000 mcg Lyophilized Vial

Kate has shared a file

WEIGHTLOSS

OBESITY
Weight management adheres to a multi-faceted lifestyle model that’s comprised of several interrelated decisions and activities such as: eating healthy foods; understanding portion sizes, nutritional values, and macronutrient ratios; creating a holistic exercise regimen that works with your schedule, incorporates your interests, is dynamic enough to prevent burnout, and sets reasonable goals; and accessing the wealth of safe, clinically proven, prescription weight management medications that are currently available. Formulation Compounding Center is dedicated to providing the resources health professionals need to aid their patients in achieving and maintaining ideal body weight goals, as they strive to improve their health-related conditions and overall quality of life.

Obesity and its many serious comorbidities exert a heavy toll in both human and economic terms. More than one-third of adults in the United States are obese, which exponentially increases their odds of hypertension, dyslipidemia, diabetes, and other cardiovascular disease risk factors. Studies have demonstrated that weight loss of as little as 5% to 10% of baseline body weight, has been shown to result in lower triglyceride and blood pressure levels, and in as much as a 58% reduction in the risk of diabetes in pre-diabetic patients. Unfortunately, the problem of obesity is typically exacerbated by aging, as this condition becomes even more difficult to control for older segments of the population. It is a mistake to merely think of obesity in relation to internal health conditions, because it impacts many other areas of one’s childhood, teen, adult, and especially senior life.  One study of individuals aged 65 years and older found that obese individuals had a 31% higher incidence of falling.

Symptoms and Causes of Obesity

The definitions for being overweight and obese vary depending on the source. The National Heart, Lung, and Blood Institute describes some of the signs of being overweight and possibly obese as: clothes feeling tight and requiring larger size; the development of extra fat around the waist; and possessing a higher than normal body mass index and waist circumference.

More specifically, with regard to defining obesity, the Mayo Clinic quantifies obesity as a body mass index (BMI) of 30 or higher. Your body mass index is calculated by dividing your weight in kilograms (kg) by your height in meters (m) squared.

Causes of Obesity

Although there are genetic components and hormonal influences, obesity occurs when you take in more calories than you burn through normal daily activities and extracurricular exercise. The body stores these excess calories as fat, which if it continues to accumulate results in obesity that can be caused by a combination of contributing factors including:

• Inactivity – a sedentary lifestyle makes it easy to overeat.
• Unhealthy diet and eating habits – frequent: high calorie meals; fast food; breakfast skipping; late night eating; drinking high calorie beverages; and eating oversized portions all contribute to weight gain.
• Pregnancy – Many women view this as a time of overindulgence, which initiates obesity, whereas others simply find this weight difficult to lose after giving birth.
• Lack of sleep – getting less than seven hours of sleep a night can cause changes in hormones that increase your appetite, and create cravings for high calorie foods.
• Certain medications – some antidepressants, anti-seizure medications, diabetes medications, antipsychotic medications, steroids, and beta blockers.
• Medical problems – specific medical diseases and conditions promote weight gain, such as Prader-Willi syndrome, Cushing’s syndrome, polycystic ovary syndrome, metabolic syndrome, etc.

Dangerous Weight Loss Drugs

• Overweight and obese individuals have been seeking quick fixes for centuries. Called ‘fat reducers’, the first diet pills emerged in the late 1800’s. Based on thyroid extract, which can increase metabolic rate, they were effective but had harsh side effects including abnormal heartbeats, increased heart rate, weakness, chest pains, high blood pressure, and fatalities. In the 1930s, a new medication (though technically a poison) called dinitrophenol became a popular for its thermogenic fat loss property (actually a symptom of phenol poisoning). Once its other poisonous symptoms (severe rashes, cataracts, peripheral neuritis, etc.) turned tragic it was removed from the market.
• A mid-1950s stimulant used in WWII to keep soldiers alert, amphetamines, promoted energy, suppressed appetite, and provided a slimming effect, but were neurologically and psychological addictive. 1965’s obesity treatment, aminorex fumarate, triggered pulmonary hypertension. By the late 1960s a form of thyroid hormone was introduced, often used in conjunction with diuretics, laxatives, and amphetamines. These drugs proved too toxic. In the 1970s, a Danish physician used ephedrine in combination with caffeine to treat asthma, and eventually weight loss. It was soon banned by several states in the 1990s and finally the U.S. Food and Drug Administration (FDA) on December 31, 2003 for adverse cardiovascular and neurological problems, and implication in several deaths.
• Later phenylpropanolamine, an ephedra derivative, became popular as an appetite suppressant. It was also discontinued due to hemorrhagic stroke and increased hypertension.
• In 1973 the FDA approved weight loss drug fenfluramine gained popularity in 1992, when it was combined with another drug, phentermine and came to be known as Fen-Phen. Boasting over 18,000,000 sold bottles in 1996 alone, pulmonary hypertension, heart lesions, and valve abnormalities caused its removal…subsequently fenfluramine was voluntarily removed from the market in 1997.

Apply 1/4 – 1/2 mL of cream onto clitoris and/or external genital 15-30 minutes prior to sex. Arousal Cream should be massaged gently into the area until it is completely absorbed. Duration of effect is 30 minutes to 2 hours and reapplication may occur as needed.

Make sure to talk to your physician or pharmacist about how frequently you should be using Arousal Cream and how much you should apply.

Arousal Cream promotes blood flow to the applied area to improve sensitivity and rates of orgasm: it does not produce an orgasm. If not completely absorbed, it may cause irritation with your partner.

Arousal Cream is formulated to act locally so side effects are minimal, but may include skin irritation, headache, dizziness, and restlessness. However, possible side effects include but are not limited to those of each of Arousal Cream’s components. The side effects of these compounds in combination have not been studied.

Call your health care provider immediately if you are experiencing any signs of an allergic reaction: skin rash, itching or hives, swelling of the face, lips, or tongue, blue tint to skin, chest tightness, pain, difficulty breathing, wheezing, dizziness, red, swollen painful area on the leg.

Arousal Cream acts synergistically via six distinct pharmacologically active compounds and each has its own list of compounds it interacts with. Interactions resulting from the combination of these compounds have not been studied and may include more than the sum of all compounds. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

As a testosterone-containing product, Arousal Cream is contraindicated in women who are breast-feeding.

DO NOT USE AROUSAL CREAM while pregnant or trying to become pregnant: one of Arousal Cream’s ingredients, Testosterone, is an FDA pregnancy risk category X (adverse fetal effects are expected). An alternative formulation without testosterone is available.

If you have contraindications with intercourse, you should consult your healthcare provider before using the medication and engaging in intercourse. You should not use this cream if you are allergic to any of the ingredients, have a history of genital herpes (*L-Arginine may facilitate replication of the herpes virus. An alternative formulation without L-Arginine is available.), chronic vaginal infections, or serious medical conditions such as heart disease or autoimmune disorder.

Additionally, despite acting almost exclusively locally, the contraindications for each of Arousal Cream’s compounds may apply. Provide your physician with information on Arousal Cream, as well as a list of your medical conditions before asking for a prescription.

Transdermal application results is primarily localized action. As such, the expected pharmacokinetics for each of Arousal Cream’s six compounds mimics those of the individual compounds when administered topically. The differences resulting from simultaneous application have not been studied.

Arousal Cream’s four vasodilators contribute by relaxing the vascular smooth muscles, which consequently dilates peripheral blood vessels (arteries and especially veins). Dilatation (widening) of the blood vessels promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Such medications are primarily used to treat or prevent heart disease due to arterial plaque buildup, blood clots, platelet clumping, and to increase blood flow through the coronary artery. These medications are also used to ease migraines, improve blood pressure to organs and tissues, lessen recovery time after surgery, increase immune-boosting effects, and speed up tissue repair/wound healing. However, they contribute to the Arousal Cream complex by exerting effects on the female genitalia. The same vasoactive mechanisms used by these agents to improve blood flow to the heart, lungs, and many other bodily tissues and functions, is believed to also increase vaginal blood flow during stimulation, thereby effectively aiding in the treatment of sexual dysfunctions.

Arousal Cream, which also goes by the name of Scream Cream, is a topical cream that, when applied to the clitoris or external genitalia, can increase blood flow to the applied area and has been reported to improve sensitivity and rates of orgasm. Compounded from a mixture of prescription products, Arousal Cream is designed to act locally without substantial absorption into the blood stream. This transdermal (absorbed through the skin) cream is comprised of six different medications and products which include: aminophylline, ergoloid mesylate, L-arginine, pentoxifylline, sildenafil citrate, and testosterone. This synergistic medication draws upon the properties of each ingredient (one bronchodilator, four vasodilators, and the potent sex steroid hormone testosterone) that can provide female libido (sex drive) and sexual stimulation enhancement.

Arousal 1: Aminophylline 30 mg/mL, Ergoloid Mesylate 0.5 mg/mL, Pentoxifylline 50 mg/mL, Sildenafil Citrate 10 mg/mL, Testosterone 1 mg/mL, L-Arginine 60 mg/mL 30 mL Topi-Click Dispenser

Arousal 2: Aminophylline 30 mg/mL, Ergoloid Mesylate 0.5 mg/mL, Pentoxifylline 50 mg/mL, Sildenafil Citrate 10 mg/mL, Testosterone 1 mg/mL 30 mL Topi-Click Dispenser

Arousal 3: Aminophylline 30 mg/mL, Ergoloid Mesylate 0.5 mg/mL, Pentoxifylline 50 mg/mL, Testosterone 1 mg/mL, L-Arginine 60 mg/mL 30 mL Topi-Click Dispenser

Arousal 4: Aminophylline 30 mg/mL, Ergoloid Mesylate 0.5 mg/mL, Pentoxifylline 50 mg/mL, Sildenafil Citrate 10 mg/mL, L-Arginine 60 mg/mL 30 mL Topi-Click Dispenser

Arousal 5: Aminophylline 30 mg/mL, Ergoloid Mesylate 0.5 mg/mL, Pentoxifylline 50 mg/mL, Sildenafil Citrate 10 mg/mL 30 mL Topi-Click Dispenser

There are no adequate and well-controlled studies of amitriptyline use in pregnant women; therefore, amitriptyline should only be used in pregnancy if the benefits to the mother outweigh the possible risks to the fetus. Adverse events, including CNS effects, limb deformities, and developmental delays have been reported in infants of mothers taking amitriptyline during pregnancy. Some studies in animals have shown teratogenic effects at amitriptyline doses ranging from 9 to 33 times the maximum recommended human dose (MRHD); however, other studies in animals at doses up to 13 times the MRHD have not shown teratogenicity. Tricyclic antidepressants (TCAs) cross the placenta. Neonatal complications after in utero exposure to TCAs including withdrawal symptoms, hypoglycemia, respiratory diagnoses, developmental delays, and jaundice have been reported. Withdrawal symptoms in neonates have included lethargy, cyanosis, tachypnea with respiratory acidosis, jitteriness, tremors, hypertonia, hypotonia, feeding difficulties, and seizures. Neonates exhibiting signs or symptoms of drug toxicity or withdrawal should be carefully monitored. The impact of in utero exposure to antidepressants or antipsychotics compared to no psychotropic exposure was assessed in infants 6 months of age using the Infant Neurological International Battery (INFANIB), a neuromotor exam that tests posture, tone, reflexes, and motor skills, and using a visual habituation paradigm of a neutral female face. The infants exposed to antipsychotics (n = 22) showed significantly lower INFANIB scores than those exposed to an antidepressant (n = 202) or no psychotropic drug (n = 85). There were no significant differences regarding habituation between the medication exposure groups. In a prospective trial evaluating the effects of in utero exposure to tricyclic or tetracyclic antidepressants in pediatric patients 15 to 71 months of age compared to similar non-exposed controls, exposure to antidepressants did not adversely affect IQ, language, behavior, or temperament. The effects of amitriptyline during labor and obstetric delivery are unknown. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185.

Women receiving tamoxifen for the treatment or prevention of breast cancer should be aware of possible drug-drug interactions between tamoxifen and specific antidepressant medications.  Antidepressants are used widely to treat depression and anxiety disorders in.

.

Baclofen

There are no adequate and well controlled studies of baclofen use during human pregnancy. Based on animal data, baclofen may cause fetal harm. Baclofen should only be used during pregnancy when the potential benefit to the mother outweighs the potential risk to the fetus. During administration of baclofen to animals during organogenesis at doses exceeding the maximum recommended human dose (MRHD), there were increased incidences of omphaloceles (ventral hernias), incomplete sternebral ossification, and/or unossified phalangeal nuclei of forelimbs and hindlimbs. A reduction in mean fetal weight with consequent delays in skeletal ossification was also observed. Human data are limited. In 3 cases, healthy infants were delivered by C-section after in utero exposure to intrathecal baclofen infusions (doses of 140 to 1,400 mcg/day). Follow up in 2 of the cases revealed normal development at 12 months and 24 months of age, respectively. A neonatal abstinence syndrome may occur shortly after birth in neonates following intrauterine baclofen exposure. In 1 case report, a woman received 80 mg of oral baclofen daily during pregnancy and post-partum. In order to prevent NAS, the neonate was placed on oral baclofen at initial dosage of 0.1 mg/kg/day for 4 days, followed by a daily decrease of 0.01 mg/kg/day until the drug was discontinued after 13 days. Of note, the neonate received approximately one-third of the total daily dose of baclofen from breast milk. Daily assessments for NAS were done using the modified Finnegan scoring system. Additional pharmacological intervention was not needed, and the neonate was discharged 3 days after the taper ended.  The effects of baclofen in labor and obstetric delivery are unknown.

Gabapentin

There are no adequate and well-controlled studies of gabapentin in pregnant women. Data from cohort studies describing the neonatal risks of gabapentin treatment during pregnancy are inconclusive. Gabapentin actively crosses the placenta. Among 6 neonates born to mothers who were taking gabapentin (doses ranging from 900 to 3,200 mg/day), umbilical cord-to-maternal plasma concentration ratios ranged from 1.3 to 2.11 (mean, 1.74) at delivery. Gabapentin concentrations in the neonates declined to an average of 27% (range, 12% to 36%) of cord blood concentrations at 24 hours postpartum. One infant was born premature at 33 weeks; however, all deliveries were uneventful and all neonates were born in healthy condition. In a prospective cohort study, rates of major malformations among neonates were similar between 223 pregnancies with gabapentin exposure and 223 unexposed pregnancies (4.1% exposed vs. 2.5% unexposed, p = 0.555). Major malformations included 2 ventricular septal defects, anencephaly, macrocephaly, microretrognathism, cutis marmorata, pyloric stenosis, bilateral varus clubfoot, and cryptorchidism. In all cases of major malformations, women received concomitant treatment with other medications during pregnancy; therefore, a causal relationship to gabapentin cannot be established. No major malformations occurred in neonates born to women exposed to gabapentin monotherapy during pregnancy (n = 36). There were higher rates of preterm births (10.5% vs. 3.9%, p = 0.019), low birth weight (less than 2,500 g) (10.5% vs. 4.4%, p = 0.033), and admission to neonatal intensive care or special care nursery (38% vs. 2.9%, p less than 0.001) among neonates with gabapentin exposure compared to unexposed neonates. Two cases of possible poor neonatal adaptation syndrome occurred in neonates with gabapentin exposure late in pregnancy compared to no cases among unexposed infants; these 2 neonates were also exposed to other psychotropic medications. In a cohort of 39 women who were exposed to gabapentin during their first trimester (97%) and throughout gestation (81.8%), malformations occurred in 3 of 44 live births. Hypospadia was reported in a neonate exposed to gabapentin and valproate; a missing kidney occurred in a neonate exposed to gabapentin and phenobarbital, and a minor malformation of the left external ear canal and 2 small skin tags at the jaw occurred in a neonate exposed to gabapentin and lamotrigine. Since exposure to multiple antiepileptic drugs occurred during these pregnancies, a causal relationship to gabapentin cannot be established. No malformations occurred in 11 patients exposed to gabapentin monotherapy during pregnancy. In animal studies, gabapentin has been fetotoxic during organogenesis at doses of 1 to 4 times the maximum recommended human dose on a mg/m2 basis. Delayed ossification of bones in the skull, limbs, and vertebrae were reported when pregnant mice received oral gabapentin (500, 1,000, or 3,000 mg/kg/day) during organogenesis. The no-effect dose for toxicity (500 mg/kg/day) is less than the maximum human recommended dose (MRHD) of 3,600 mg/kg on a body surface area (mg/m2) basis. Increased incidences of hydroureter and/or hydronephrosis were observed at all doses tested in studies in which rats received oral gabapentin (500 to 2,000 mg/kg/day). An increased incidence of fetal loss was also noted at all doses tested when pregnant rabbits were treated with oral gabapentin (60, 300, or 1,500 mg/kg) during organogenesis. Physicians are advised to recommend that pregnant patients receiving gabapentin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug. Patients must call 1-888-233-2334 to enroll in the registry.

Amitriptyline

There are no adequate and well-controlled studies of amitriptyline use in pregnant women; therefore, amitriptyline should only be used in pregnancy if the benefits to the mother outweigh the possible risks to the fetus. Adverse events, including CNS effects, limb deformities, and developmental delays have been reported in infants of mothers taking amitriptyline during pregnancy. Some studies in animals have shown teratogenic effects at amitriptyline doses ranging from 9 to 33 times the maximum recommended human dose (MRHD); however, other studies in animals at doses up to 13 times the MRHD have not shown teratogenicity. Tricyclic antidepressants (TCAs) cross the placenta. Neonatal complications after in utero exposure to TCAs including withdrawal symptoms, hypoglycemia, respiratory diagnoses, developmental delays, and jaundice have been reported. Withdrawal symptoms in neonates have included lethargy, cyanosis, tachypnea with respiratory acidosis, jitteriness, tremors, hypertonia, hypotonia, feeding difficulties, and seizures. Neonates exhibiting signs or symptoms of drug toxicity or withdrawal should be carefully monitored. The impact of in utero exposure to antidepressants or antipsychotics compared to no psychotropic exposure was assessed in infants 6 months of age using the Infant Neurological International Battery (INFANIB), a neuromotor exam that tests posture, tone, reflexes, and motor skills, and using a visual habituation paradigm of a neutral female face. The infants exposed to antipsychotics (n = 22) showed significantly lower INFANIB scores than those exposed to an antidepressant (n = 202) or no psychotropic drug (n = 85). There were no significant differences regarding habituation between the medication exposure groups. In a prospective trial evaluating the effects of in utero exposure to tricyclic or tetracyclic antidepressants in pediatric patients 15 to 71 months of age compared to similar non-exposed controls, exposure to antidepressants did not adversely affect IQ, language, behavior, or temperament. The effects of amitriptyline during labor and obstetric delivery are unknown. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at

http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants 

Clinical Update 2019: Tamoxifen and Antidepressants – MGH Center for Women’s Mental Health

Women receiving tamoxifen for the treatment or prevention of breast cancer should be aware of possible drug-drug interactions between tamoxifen and specific antidepressant medications.  Antidepressants are used widely to treat depression and anxiety disorders in […]

.

Baclofen

There are no adequate and well controlled studies of baclofen use during human pregnancy. Based on animal data, baclofen may cause fetal harm. Baclofen should only be used during pregnancy when the potential benefit to the mother outweighs the potential risk to the fetus. During administration of baclofen to animals during organogenesis at doses exceeding the maximum recommended human dose (MRHD), there were increased incidences of omphaloceles (ventral hernias), incomplete sternebral ossification, and/or unossified phalangeal nuclei of forelimbs and hindlimbs. A reduction in mean fetal weight with consequent delays in skeletal ossification was also observed. Human data are limited. In 3 cases, healthy infants were delivered by C-section after in utero exposure to intrathecal baclofen infusions (doses of 140 to 1,400 mcg/day). Follow up in 2 of the cases revealed normal development at 12 months and 24 months of age, respectively. A neonatal abstinence syndrome may occur shortly after birth in neonates following intrauterine baclofen exposure. In 1 case report, a woman received 80 mg of oral baclofen daily during pregnancy and post-partum. In order to prevent NAS, the neonate was placed on oral baclofen at initial dosage of 0.1 mg/kg/day for 4 days, followed by a daily decrease of 0.01 mg/kg/day until the drug was discontinued after 13 days. Of note, the neonate received approximately one-third of the total daily dose of baclofen from breast milk. Daily assessments for NAS were done using the modified Finnegan scoring system. Additional pharmacological intervention was not needed, and the neonate was discharged 3 days after the taper ended.  The effects of baclofen in labor and obstetric delivery are unknown.

Gabapentin

There are no adequate and well-controlled studies of gabapentin in pregnant women. Data from cohort studies describing the neonatal risks of gabapentin treatment during pregnancy are inconclusive. Gabapentin actively crosses the placenta. Among 6 neonates born to mothers who were taking gabapentin (doses ranging from 900 to 3,200 mg/day), umbilical cord-to-maternal plasma concentration ratios ranged from 1.3 to 2.11 (mean, 1.74) at delivery. Gabapentin concentrations in the neonates declined to an average of 27% (range, 12% to 36%) of cord blood concentrations at 24 hours postpartum. One infant was born premature at 33 weeks; however, all deliveries were uneventful and all neonates were born in healthy condition. In a prospective cohort study, rates of major malformations among neonates were similar between 223 pregnancies with gabapentin exposure and 223 unexposed pregnancies (4.1% exposed vs. 2.5% unexposed, p = 0.555). Major malformations included 2 ventricular septal defects, anencephaly, macrocephaly, microretrognathism, cutis marmorata, pyloric stenosis, bilateral varus clubfoot, and cryptorchidism. In all cases of major malformations, women received concomitant treatment with other medications during pregnancy; therefore, a causal relationship to gabapentin cannot be established. No major malformations occurred in neonates born to women exposed to gabapentin monotherapy during pregnancy (n = 36). There were higher rates of preterm births (10.5% vs. 3.9%, p = 0.019), low birth weight (less than 2,500 g) (10.5% vs. 4.4%, p = 0.033), and admission to neonatal intensive care or special care nursery (38% vs. 2.9%, p less than 0.001) among neonates with gabapentin exposure compared to unexposed neonates. Two cases of possible poor neonatal adaptation syndrome occurred in neonates with gabapentin exposure late in pregnancy compared to no cases among unexposed infants; these 2 neonates were also exposed to other psychotropic medications. In a cohort of 39 women who were exposed to gabapentin during their first trimester (97%) and throughout gestation (81.8%), malformations occurred in 3 of 44 live births. Hypospadia was reported in a neonate exposed to gabapentin and valproate; a missing kidney occurred in a neonate exposed to gabapentin and phenobarbital, and a minor malformation of the left external ear canal and 2 small skin tags at the jaw occurred in a neonate exposed to gabapentin and lamotrigine. Since exposure to multiple antiepileptic drugs occurred during these pregnancies, a causal relationship to gabapentin cannot be established. No malformations occurred in 11 patients exposed to gabapentin monotherapy during pregnancy. In animal studies, gabapentin has been fetotoxic during organogenesis at doses of 1 to 4 times the maximum recommended human dose on a mg/m2 basis. Delayed ossification of bones in the skull, limbs, and vertebrae were reported when pregnant mice received oral gabapentin (500, 1,000, or 3,000 mg/kg/day) during organogenesis. The no-effect dose for toxicity (500 mg/kg/day) is less than the maximum human recommended dose (MRHD) of 3,600 mg/kg on a body surface area (mg/m2) basis. Increased incidences of hydroureter and/or hydronephrosis were observed at all doses tested in studies in which rats received oral gabapentin (500 to 2,000 mg/kg/day). An increased incidence of fetal loss was also noted at all doses tested when pregnant rabbits were treated with oral gabapentin (60, 300, or 1,500 mg/kg) during organogenesis. Physicians are advised to recommend that pregnant patients receiving gabapentin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug. Patients must call 1-888-233-2334 to enroll in the registry.

Amitriptyline

Amitriptyline is contraindicated in patients with a hypersensitivity to amitriptyline or any of its inactive ingredients. Patients with a hypersensitivity to amitriptyline may experience a tricyclic antidepressant hypersensitivity reaction to other tricyclics. In some case reports, cross-allergenicity did not occur in patients who experienced a rash from the primary tricyclic and were switched to an alternate tricyclic. However, because the data are too limited to be conclusive, it is generally advisable to substitute with an antidepressant from another class in patients with a known hypersensitivity to amitriptyline. When considering use of an alternate tricyclic, it is prudent to avoid other cyclic compounds if the patient has experienced a severe or life-threatening reaction to the primary agent. Cross-sensitivity is possible in patients with a carbamazepine hypersensitivity. The manufacturer of carbamazepine contraindicates use in patients with a hypersensitivity to tricyclic compounds. The potential for cross-reactivity between tricyclics and other structurally similar compounds such as cyclobenzaprine or tetracyclic antidepressants (e.g., maprotiline, amoxapine) has not been established.

Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) simultaneously; use with MAOI therapy is contraindicated. When it is desired to replace MAOI therapy with amitriptyline, a minimum of 14 days should be allowed to elapse after the MAOI is discontinued. Amitriptyline should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved.

Amitriptyline is contraindicated in patients who are in the acute recovery phase following acute myocardial infarction; use of amitriptyline could cause sudden death. Amitriptyline may cause orthostatic hypotension, particularly in the initial dosing titration. Use tricyclic antidepressants (TCAs) with caution and with close monitoring in patients with any cardiac disease (e.g., heart failure, history of myocardial infarction, congenital heart disease). TCAs, including amitriptyline, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time. Myocardial infarction and stroke have been reported with drugs of this class. Although the risk of cardiovascular adverse events is higher after acute overdose, patients with cardiovascular disease should be closely monitored via ECGs and clinical exams. TCAs should not be given to patients with QT prolongation. Use amitriptyline with caution in patients with conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes, thyroid impairment, malnutrition, a history of alcohol abuse, or hepatic impairment may also be at increased risk for QT prolongation. Rarely, TCAs are used in pediatric patients for the treatment of attention-deficit hyperactivity disorder (ADHD). There have been reports of sudden death in pediatric patients treated with TCAs that were not associated with overdoses. Although cardiac monitoring is recommended, it is unclear whether monitoring can prevent a sudden death event. The American Heart Association recommends conducting a detailed patient and family history and physical examination prior to initiating ADHD pharmacologic treatment, and obtaining a baseline ECG is a reasonable addition to the initial evaluation. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history. If a child or adolescent has any significant findings on physical examination, ECG, or family history, a pediatric cardiologist should be consulted before the medication is initiated.

Amitriptyline should be used with caution in children with a known family history of heart disease or who are taking medications that cause QT prolongation. QTc interval prolongation, tachycardias, and other side effects have been reported in children who have taken tricyclic antidepressants (TCAs); there are rare reports of deaths due to cardiovascular side effects. Routine cardiovascular monitoring has been suggested for children receiving TCAs due to the potential of these agents to produce adverse cardiac effects.

All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. If a patient develops manic symptoms, amitriptyline should be withheld and appropriate therapy initiated to treat the manic symptoms. Additionally, depression may be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients should be adequately screened for bipolar disorder prior to initiating an antidepressant. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Also use TCAs with caution in patients with psychotic disorders (e.g., schizophrenia). Psychotic symptoms may be precipitated in some individuals. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes. Caregivers should be advised to closely observe the patient on a daily basis and to communicate immediately with the prescriber the emergence of unusual changes in behavior or suicidality. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. It should be noted that amitriptyline is not approved for use in treating bipolar depression.

Amitriptyline can induce significant sedation, particularly during the initiation of treatment. Amitriptyline may enhance the response to alcohol, the effects of barbiturates, and increase sedation or central nervous system (CNS) effects during coadministration with other CNS depressants. Patients should use caution with ethanol ingestion. In patients who may use alcohol excessively (e.g., alcoholism), the potentiation of CNS effects may increase the danger inherent in any suicide attempt or overdosage. Patients should use caution when driving or operating machinery until they are aware of the effects of the medication.

Amitriptyline should be used with extreme caution in patients with a preexisting seizure disorder because tricyclic antidepressants (TCAs) can lower the seizure threshold. If seizures occur during TCA therapy, the TCA should be discontinued. Concurrent administration of amitriptyline and electroconvulsive therapy (ECT) may increase the hazards associated with such therapy. Such treatment should be limited to patients for whom it is essential.

Tricyclic antidepressants (TCAs), such as amitriptyline, should be used with caution in patients with hepatic disease. Metabolism of tricyclic antidepressants may be altered in patients with hepatic impairment. Rarely, TCAs have caused hepatitis and jaundice, which are reversible on discontinuation. Liver function tests (LFTs) should be performed if symptoms occur and the drug discontinued if there is persistent elevation of enzymes.

Amitriptyline should be discontinued several days before elective surgery because of the risk of adverse reactions during surgery, including increased sensitivity to catecholamines and potential cardiovascular reactions.

The anticholinergic effects of tricyclic antidepressants (TCAs) limit the use of the drugs in certain patients. The anticholinergic effects of amitriptyline may be significant and are additive with other anticholinergic medications. These actions can decrease GI motility, causing constipation and in some cases, paralytic ileus. Patients who have risk factors for urinary retention, such as those with benign prostatic hypertrophy, should also be treated with caution. Anticholinergic effects appear most frequently and cause the greatest morbidity in elderly patients.

Caution is recommended when prescribing amitriptyline to patients with closed-angle glaucoma. The pupillary dilation that can occur with antidepressants may precipitate a closed-angle glaucoma attack in patients with anatomically narrow angles who do not have a patent iridectomy. An acute attack of closed-angle glaucoma is considered a medical emergency because the increased intraocular pressure is rapid and severe, and may quickly result in blindness if left untreated 

The anticholinergic effects of amitriptyline may increase lens discomfort for wearers of contact lenses. Mydriasis, disturbance of accommodation, and dry eyes may contribute to blurred vision and lens intolerance. The use of lubricating drops may be necessary.

Patients who develop a continued fever and a sore throat during therapy with a tricyclic antidepressant (TCA) should have leukocyte and differential blood counts performed. The TCA should be discontinued if there is evidence of pathological neutrophil depression. On rare occasions, there have been reports of leukopenia, agranulocytosis, neutropenia, thrombocytopenia, anemia, and pancytopenia in association with TCA use.

Tricyclic antidepressants (TCAs) like amitriptyline should be used with caution in patients who have thyroid disease. Close supervision is required when amitriptyline is given to patients with hyperthyroidism or those patients with hypothyroidism who are receiving thyroid medication.

Tricyclic antidepressants (TCAs) affect blood glucose concentrations because of their effect on the endocrine system; both elevation and lowering of blood sugar levels have been reported. Therefore, amitriptyline should be used with caution in patients with diabetes mellitus. TCAs should also be used with caution in patients with tumors of the adrenal medulla (e.g., pheochromocytoma, neuroblastoma) in whom these drugs may provoke hypertensive crises.

Tricyclic antidepressants lower the seizure threshold. Because of a potential increased risk of seizures, amitriptyline should not be used during intrathecal radiographic contrast administration. Tricyclic antidepressant therapy should be discontinued 48 hours before and not restarted for at least 24 hours after myelography.

Patients may be more prone to sunburn during therapy with amitriptyline. Patients should avoid excessive exposure to sunlight since there have been reports of photosensitization during the use of tricyclic antidepressants (TCAs). Suitable precautions should be taken to limit effects prior to sunlight (UV) exposure, such as wearing long-sleeved clothing and a hat, and using sunscreens.

Following prolonged therapy, abrupt discontinuation of a tricyclic antidepressant (TCA) should be avoided because it could precipitate a drug discontinuation syndrome. Symptoms of cholinergic rebound such as nausea, vomiting, or diarrhea may occur. Other typical symptoms of antidepressant discontinuation syndrome include flu-like symptoms, insomnia, imbalance, sensory disturbances, and hyperarousal.

Amitriptyline dose selection should generally be cautious in the geriatric patient. Initiation at the low end of the dosage range with slow titration and careful observation is recommended. Geriatric patients are particularly sensitive to the peripheral and central anticholinergic side effects of amitriptyline and may be at increased risk for falls. According to the Beers Criteria, tricyclic antidepressants (TCAs) are considered potentially inappropriate medications (PIMs) in geriatric patients; avoid TCA use due to the potential for orthostatic hypotension, anticholinergic effects or toxicity (e.g., constipation, urinary difficulties, blurred vision, dry mouth, delirium), or sedation. Avoid TCA use in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: syncope (increased risk of orthostatic hypotension or bradycardia), dementia/cognitive impairment (drug-induced CNS effects), delirium/high risk of delirium (new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (urinary retention or hesitancy). Further, the Beers expert panel recommends avoiding TCAs in elderly patients with a history of falls or fractures, unless safer alternatives are not available, since TCAs can produce ataxia, impaired psychomotor function, syncope, and additional falls. If amitriptyline must be used in an elderly patient with a history of falls or fractures, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Lastly, TCAs can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions. Sodium levels should be closely monitored when starting or changing dosages of TCAs in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities; the duration of therapy should be in accordance with pertinent literature and clinical practice guidelines. TCAs are rarely the medications of choice in the elderly because of strong anticholinergic and sedating properties. However, TCAs may be appropriate in residents being treated for neurogenic pain when the benefits outweigh the risks and safer medications or interventions are either not indicated or have been considered, attempted, and failed. All residents being treated for depression with any antidepressant should be monitored closely for worsening of depression and/or suicidal behavior or thinking, especially during initiation of therapy and during dose changes. Antidepressants may cause dizziness, nausea, diarrhea, anxiety, nervousness, insomnia, somnolence, weight gain, anorexia, or increased appetite. Many of these effects can increase the risk for falls. Prior to discontinuation, many antidepressants may need a taper to avoid a withdrawal syndrome. Monitoring should consist of a review for continued need at least quarterly, and documentation of the rationale for continuation. When the drug is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated.

Tobacco smoking has been shown to increase the clearance of tricyclic antidepressants (TCAs), including amitriptyline, by inducing hepatic microsomal enzymes. The effect of tobacco on hepatic microsomal enzymes is not related to the nicotine component, so sudden smoking cessation may result in a reduced clearance of amitriptyline and increased amitriptyline effects, despite the initiation of nicotine replacement products.

Baclofen

Geriatric patients or patients with cerebral lesions as opposed to spinal lesions may experience increased toxicity to baclofen. Elderly patients require lower initial doses and slow dose titration. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities. According to the OBRA guidelines, most muscle relaxants are poorly tolerated by older adults due to anticholinergic side effects, sedation, and/or weakness. However, periodic use (e.g., once every 3 months) for no more than 7 days may be appropriate when other interventions or alternative medications are not effective or indicated. Chronic use in individuals with complications due to multiple sclerosis, spinal cord injuries, cerebral palsy, and other select conditions may be indicated, although close monitoring is warranted. Abrupt discontinuation of some muscle relaxants may cause or predispose individuals to seizures or hallucinations.

Patients with pre-existing psychiatric disorders (e.g., bipolar disorder, depression, psychosis, schizophrenia) are at increased risk for baclofen-induced psychiatric adverse reactions.

Hyperglycemia is associated with oral and intrathecal baclofen use. Use with appropriate caution in patients with diabetes mellitus.

Baclofen has caused deterioration in the control of seizures and EEG changes in patients with epilepsy. Baclofen should be prescribed cautiously to patients with a history of a seizure disorder or a history of seizures.

Cases of baclofen toxicity (manifesting as encephalopathy, abdominal pain, and in some cases, seizures and respiratory depression) have been reported in patients with severe renal impairment (e.g., serum creatinine more than 2 mg/dL) and renal failure who received oral baclofen. Most patients who became toxic received low oral doses of baclofen (e.g., 15 to 30 mg/day) for a short duration. Baclofen toxicity can occur with relatively low doses within 24 to 48 hours of initiation of oral therapy. In renal failure patients receiving dialysis, doses not exceeding 5 mg/day orally have been suggested; although toxicity may still occur. Therefore, in patients with severe renal impairment or renal failure, alternative therapies should be considered. If a patient develops baclofen toxicity, hemodialysis may be a useful treatment to alleviate clinical symptoms.Similar toxicity is not expected with intrathecal use of baclofen as resultant drug plasma concentrations are 100-fold lower then those experienced with oral use.

Patients should be warned that baclofen may impair the ability to perform certain tasks that require mental alertness or physical coordination such as driving or operating machinery. Patients should also be cautioned that the central nervous system (CNS) depressant effects of baclofen may be additive to those of ethanol ingestion and coadministration with other CNS depressants.

Gabapentin

Monitor all patients beginning treatment with antiepileptic drugs (AEDs) or currently receiving gabapentin closely for emerging or worsening depression or suicidal ideation. Advise patients and caregivers of the increased risk of suicidal thoughts and behaviors and to immediately report the emergence of new or worsening of depression, suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. AEDs should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any patient may be related to the illness being treated. There is an increased risk of suicidal ideation and behavior in patients receiving AEDs to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). Gabapentin is known to be substantially excreted by the kidney. Adjust the gabapentin dose in patients with renal impairment or renal failure undergoing dialysis, such as hemodialysis.

Because gabapentin causes somnolence and dizziness, advise patients against driving or operating machinery until they have gained enough experience on gabapentin to assess whether gabapentin impairs their ability to perform such tasks. Driving performance studies conducted with a prodrug of gabapentin (gabapentin enacarbil) indicate that gabapentin may cause significant driving impairment. The patients’ ability to assess their own driving competence, as well as their ability to assess the degree of somnolence caused by gabapentin, can be imperfect. The duration of driving impairment after starting therapy with gabapentin is unknown. Whether the impairment is related to somnolence or other effects of gabapentin is unknown.

When using gabapentin, carefully evaluate patients for a history of substance abuse and monitor for signs and symptoms of gabapentin misuse or abuse (e.g., development of tolerance, self-dose escalation, and drug-seeking behavior). A small number of postmarketing cases report gabapentin misuse and abuse.

Initiate gabapentin at the lowest recommended dose and monitor for symptoms of respiratory depression and sedation in elderly patients, patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD), and during coadministration with other CNS depressants. Serious, life-threatening, and fatal respiratory depression has been reported with gabapentin. Most cases involved coadministration of another CNS depressant, particularly opioids, in patients with underlying respiratory impairment or advanced age. Respiratory depression, if left untreated, may cause respiratory arrest and death. Management of respiratory depression should include observation, necessary supportive measures, and reduction or withdrawal of CNS depressants, including gabapentin. Taper the dose of gabapentin used for analgesia or seizure control before discontinuation

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

Amitriptyline Hydrochloride / Baclofen / Gabapentin Vaginal Cream may relieve symptoms associated with vulvodynia and Provoked Vestibuladynia.

This cream is formulated to act locally so side effects are generally minimal, but may include skin irritation, headache, dizziness, and somnolence. However, possible side effects include but are not limited to those of each of the cream’s components. The side effects of these compounds in combination have not been studied.

Call your health care provider immediately if you are experiencing any signs of an allergic reaction: skin rash, itching or hives, swelling of the face, lips, or tongue, blue tint to skin, chest tightness, pain, difficulty breathing, wheezing, dizziness, red, swollen painful area on the leg.