Desoxyn

Methamphetamine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• restlessness
• upset stomach
• constipation
• dry mouth
• unpleasant taste
• headache
• weight loss
• loss of appetite
• itching
• changes in sex drive or ability
• difficulty falling asleep or staying asleep

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, stop taking methamphetamine and call your doctor immediately or get emergency medical treatment:

• fast or pounding heartbeat
• uncontrollable shaking of a part of your body
• excessive tiredness
• slow or difficult speech
• seizures
• motor or verbal tics
• believing things that are not true
• feeling unusually suspicious of others
• hallucinating (seeing things or hearing voices that do not exist)
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
• mania (frenzied or abnormally excited mood)
• aggressive or hostile behavior
• changes in vision or blurred vision
• paleness or blue color of fingers or toes
• pain, burning, or tingling in the hands or feet
• unexplained wounds appearing on fingers or toes

Methamphetamine may slow children's growth or weight gain. Your child's doctor will watch his or her growth carefully. Talk to your child's doctor if you have concerns about your child's growth or weight gain while he or she is taking this medication. Talk to your child's doctor about the risks of giving methamphetamine to your child.

Methamphetamine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

• Desoxyn^®

Pregnancy Category: C

Lactation: do not nurse

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Amphetamine anorexigenic agent; sympathomimetic amine related to ephedrine and amphetamine with CNS stimulant activity; causes release of dopamine and other catechoamines from their storage in the presynaptic nerve terminals; inhibits monoamine transporters and oxidase, causing reuptake and metabolism of catecholamines

Pharmacokinetics

Half-Life: 4-5 hr

Absorption: Rapid

Metabolism: Liver

Excretion: Urine, varies with pH

Desoxyn is part of the drug class:

• Centrally acting sympathomimetics

You should not use this medicine if you have glaucoma, overactive thyroid, severe agitation, moderate to severe high blood pressure, heart disease or coronary artery disease, or a history of drug abuse.

Methamphetamine may be habit-forming, and this medicine is a drug of abuse. Tell your doctor if you have had problems with drug or alcohol abuse.

Stimulants have caused stroke, heart attack, and sudden death in people with high blood pressure, heart disease, or a heart defect.

Do not use methamphetamine if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine.

Methamphetamine may cause new or worsening psychosis (unusual thoughts or behavior), especially if you have a history of depression, mental illness, or bipolar disorder.

You may have blood circulation problems that can cause numbness, pain, or discoloration in your fingers or toes.

Call your doctor right away if you have: signs of heart problems--chest pain, feeling light-headed or short of breath; signs of psychosis--paranoia, aggression, new behavior problems, seeing or hearing things that are not real; signs of circulation problems--unexplained wounds on your fingers or toes.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid drinking fruit juices or taking vitamin C at the same time you take methamphetamine. These can make your body absorb less of the medicine.

Ask your doctor before using a stomach acid medicine (including Alka-Seltzer or sodium bicarbonate). Some of these medicines can change the way your body absorbs methamphetamine, and may increase side effects.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• medication to treat depression or mental illness;

• insulin;

• blood pressure medicine; or

• seizure medicine.

This list is not complete. Other drugs may interact with methamphetamine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Dextrorotatory isomer of phenylmethylamine;a sympathomimetic amine with CNS-stimulating activity.c

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• A fast heartbeat.
• A heartbeat that does not feel normal.
• Shakiness.
• Restlessness.
• Very nervous and excitable.
• Change in sex ability.
• Lowered interest in sex.
• Seizures.
• For males, erections (hard penis) that happen often or that last a long time.
• Change in color of hands or feet from pale to blue or red.
• Numbness, pain, tingling, or cold feeling of the hands or feet.
• Any sores or wounds on the fingers or toes.
• Dark urine.
• Not able to pass urine or change in how much urine is passed.
• Muscle pain or weakness.
• Heart attacks, strokes, and sudden deaths have happened in adults taking this medicine. Sudden deaths have also happened in children with very bad heart problems or heart defects. Call your doctor right away if you have a change in strength on 1 side that is greater than the other, trouble speaking or thinking, change in balance, drooping on 1 side of the face, change in eyesight, chest pain or pressure, shortness of breath, or very bad dizziness or passing out.

Methamphetamine is a sympathomimetic amine with CNS stimulant activity. Peripheral actions include elevation of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics”. It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions, or metabolic effects, may be involved, for example.

Adult obese subjects instructed in dietary management and treated with “anorectic” drugs, lose more weight on the average than those treated with placebo and diet, as determined in relatively short-term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The origins of the increased weight loss due to the various possible drug effects are not established. The amount of weight loss associated with the use of an “anorectic” drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.

In humans, methamphetamine is rapidly absorbed from the gastrointestinal tract. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine. The biological half-life has been reported in the range of 4 to 5 hours. Excretion occurs primarily in the urine and is dependent on urine pH. Alkaline urine will significantly increase the drug half-life. Approximately 62% of an oral dose is eliminated in the urine within the first 24 hours with about one-third as intact drug and the remainder as metabolites.

The following are adverse reactions in decreasing order of severity within each category that have been reported:

Cardiovascular: Elevation of blood pressure, tachycardia and palpitation. Fatal cardiorespiratory arrest has been reported, mostly in the context of abuse/misuse.

Central Nervous System: Psychotic episodes have been rarely reported at recommended doses. Dizziness, dysphoria, overstimulation, euphoria, insomnia, tremor, restlessness and headache. Exacerbation of motor and phonic tics and Tourette’s syndrome.

Gastrointestinal: Diarrhea, constipation, dryness of mouth, unpleasant taste and other gastrointestinal disturbances.

Hypersensitivity: Urticaria.

Endocrine: Impotence and changes in libido; frequent or prolonged erections.

Musculoskeletal: Rhabdomyolysis.

Miscellaneous: Suppression of growth has been reported with the long-term use of stimulants in children (see WARNINGS).

Skin and Subcutaneous Tissue Disorders: Alopecia.

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Applies to methamphetamine: oral tablet, oral tablet extended release

Along with its needed effects, methamphetamine (the active ingredient contained in Desoxyn) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking methamphetamine:

• Agitation
• delusions
• hallucinations

• Blurred vision
• chest discomfort or pain
• dark-colored urine
• difficulty breathing
• dizziness
• faintness
• false or unusual sense of wellbeing
• fast, pounding, or irregular heartbeat or pulse
• fever
• headache
• muscle cramps or spasms
• muscle pain or stiffness
• pounding in the ears
• restlessness
• shakiness in the legs, arms, hands, or feet
• swelling of the feet or lower legs
• trembling or shaking of the hands or feet
• trouble sleeping
• twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• uncontrolled vocal outbursts and tics
• unusual tiredness or weakness

Some side effects of methamphetamine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bad, unusual, or unpleasant (after) taste
• change in taste
• constipation
• decreased interest in sexual intercourse
• dry mouth
• hives or welts, itching, or skin rash
• inability to have or keep an erection
• indigestion
• loss in sexual ability, desire, drive, or performance
• passing of gas
• redness of the skin
• weight loss

Summary of Use during Lactation

Because there is no published experience with methamphetamine as a therapeutic agent during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Methamphetamine should not be used as a recreational drug by nursing mothers because it may impair their judgment and child care abilities. Methamphetamine and its metabolite, amphetamine, are detectable in breastmilk and infant's serum after abuse of methamphetamine by nursing mothers. However, these data are from random collections rather than controlled studies because of ethical considerations in administering recreational methamphetamine to nursing mothers. Other factors to consider are the possibility of positive urine tests in breastfed infants which might have legal implications, and the possibility of other harmful contaminants in street drugs. In mothers who abuse methamphetamine while nursing, withholding breastfeeding for 24 to 48 hours after the maternal dose has been recommended.[1][2] However, breastfeeding is generally discouraged in mothers who are actively abusing amphetamines.[3][4][5][6]

Drug Levels

Maternal Levels. Two nursing mothers who were intravenous methamphetamine abusers collected milk samples just before methamphetamine injection and every 2 to 6 hours after injection for 24 hours. Because the drugs were illicit street drugs, the doses of methamphetamine were not known. Peak and average milk methamphetamine concentrations were about 160 mcg/L and 111 mcg/L in one woman and 610 mcg/L and 281 mcg/L in the other, respectively. Milk methamphetamine concentrations fell with half-lives of 13.6 and 7.4 hours, respectively. Amphetamine, thought to be derived from metabolism of methamphetamine, was present in relatively constant concentrations in the milk of both mothers, averaging 4 and 15 mcg/L, respectively. The authors estimated that the infants would have received 16.7 and 42.2 mcg/kg per day of methamphetamine and 0.8 and 2.5 mcg/kg per day of amphetamine, respectively.[1] These estimated mg/kg infant doses of methamphetamine are lower than therapeutic doses of the equipotent dextroamphetamine for older children with attention deficit hyperactivity disorder. However, this is not evidence of safety for breastfed infants because the data on these two women can not be extrapolated to other methamphetamine abusers.

Thirty-three mothers in Thailand were identified who had predelivery urine drug screens positive for methamphetamine. On average they used methamphetamine 2.4 times per week, primarily by smoking crushed tablets. Of these, 22 had undetectable postpartum methamphetamine milk levels. Of the 11 mothers with methamphetamine in breastmilk, only two mothers had 4 consecutive milk samples containing methamphetamine that were analyzed. The mothers had smoked methamphetamine (dosage uncertain) 53 and 68 hours prior to delivery, respectively. First milk samples contained 142 and 345 mcg/L of methamphetamine in the two mothers. The half-lives of methamphetamine in breastmilk were 11.3 and 30.3 hours, respectively. The authors estimated that in the first 24 hours after birth their exclusively breastfed infant would have received 59.3 mcg or 21.3 mcg/kg/day in the first case and 93.0 mcg or 51.7 mcg/kg/day in the second case. Methamphetamine became undetectable in breastmilk about 100 hours after the last drug use in both mothers, which was about one day prior to the mothers' urine becoming negative for methamphetamine.[2] Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

A 2-month-old infant whose mother used illicit street methamphetamine recreationally by nasal inhalation was found dead 8 hours after a small amount of breastfeeding and ingestion of 120 to 180 mL of formula. The infant's serum methamphetamine concentration on autopsy was 39 mcg/L. Although the infant's mother was convicted of child endangerment for the use of methamphetamine during breastfeeding, the role that methamphetamine played in the infant's death has been questioned because of the low infant serum methamphetamine concentration and the mother's alleged minimal breastfeeding.[7][8]

Effects on Lactation and Breastmilk

A single oral dose of 0.2 mg/kg to a maximum of 17.5 mg of d-methamphetamine was given to 6 subjects (4 male and 2 female). Serum prolactin concentrations were unchanged over a period of 300 minutes after the dose.[9]

In 2 papers by the same authors, 20 women with normal physiologic hyperprolactinemia were studied on days 2 or 3 postpartum. Eight received dextroamphetamine 7.5 mg intravenously, 6 received 15 mg intravenously and 6 who served as controls received intravenous saline. The 7.5 mg dose reduced serum prolactin by 25 to 32% compared to control, but the difference was not statistically significant. The 15 mg dose significantly decreased serum prolactin by 30 to 37% at times after the infusion. No assessment of milk production was presented. The authors also quoted data from another study showing that a 20 mg oral dose of dextroamphetamine produced a sustained suppression of serum prolactin by 40% in postpartum women.[10][11]

A study compared 31 methamphetamine-dependent subject to 23 non-dependent subjects. The serum prolactin concentrations in the methamphetamine-dependent subjects were elevated at days 2 and 30 of abstinence. The elevation was greater in women than in men.[12] The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.

In a retrospective Australian study, mothers who used intravenous amphetamines during pregnancy were less likely to be breastfeeding their newborn infants at discharge than mothers who abused other drugs (27% vs 42%). The cause of this difference was not determined.[13]

A prospective, multicenter study followed mothers who used methamphetamine prenatally (n = 204) to those who did not (n = 208). Mothers who used methamphetamine were less likely to breastfeed their infants (38%) at hospital discharge than those who did not use methamphetamine (76%).[14]

Alternate Drugs to Consider

(Therapeutic use) Amphetamine, Dextroamphetamine, Lisdexamfetamine, Methylphenidate

References

1. Bartu A, Dusci LJ, Ilett KF. Transfer of methylamphetamine and amphetamine into breast milk following recreational use of methylamphetamine. Br J Clin Pharmacol. 2009;67:455-9. PMID: 19371319

2. Chomchai C, Chomchai S, Kitsommart R. Transfer of methamphetamine (MA) into breast milk and urine of postpartum women who smoked MA tablets during pregnancy: Implications for initiation of breastfeeding. J Hum Lact. 2016;32:333-9. PMID: 26452730

3. ACOG Committee on Health Care for Underserved Women. Committee Opinion No. 479: Methamphetamine abuse in women of reproductive age. Obstet Gynecol. 2011;117:751-5. PMID: 21343793

4. Oei JL, Kingsbury A, Dhawan A et al. Amphetamines, the pregnant woman and her children: A review. J Perinatol. 2012;32:737-47. PMID: 22652562

5. AAP Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012;129:e827-41. PMID: 22371471

6. Wong S, Ordean A, Kahan M. SOGC clinical practice guidelines: Substance use in pregnancy: No. 256, April 2011. Int J Gynaecol Obstet. 2011;114:190-202. PMID: 21870360

7. Ariagno R, Karch SB, Middleberg R et al. Methamphetamine ingestion by a breast-feeding mother and her infant's death: People v Henderson. JAMA. 1995;274:215. Letter. PMID: 7609223

8. Green LS. People v Henderson: the prosecution responds. JAMA. 1996;275:183-4. Letter. PMID: 8604164

9. Gouzoulis-Mayfrank E, Thelen B, Habermeyer E et al. Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study. Psychopharmacology (Berl). 1999;142:41-50. PMID: 10102781

10. DeLeo V, Cella SG, Camanni F, Genazzani AR, Muller EE. Prolactin lowering effect of amphetamine in normoprolactinemic subjects and in physiological and pathological hyperprolactinemia. Horm Metab Res. 1983;15:439-43. PMID: 6642414

11. Petraglia F, De Leo V, Sardelli S et al. Prolactin changes after administration of agonist and antagonist dopaminergic drugs in puerperal women. Gynecol Obstet Invest. 1987;23:103-9. PMID: 3583091

12. Zorick T, Mandelkern MA, Lee B et al. Elevated plasma prolactin in abstinent methamphetamine-dependent subjects. Am J Drug Alcohol Abuse. 2011;37:62-7. PMID: 21142706

13. Oei JL, Abdel-Latif ME, Clark R et al. Short-term outcomes of mothers and infants exposed to antenatal amphetamines. Arch Dis Child Fetal Neonatal Ed. 2010;95:F36-F41. PMID: 19679891

14. Shah R, Diaz SD, Arria A et al. Prenatal methamphetamine exposure and short-term maternal and infant medical outcomes. Am J Perinatol. 2012;29:391-400. PMID: 22399214