Anagrelide hydrochloride and Naloxone Hydrochloride

• Generic Name: anagrelide
• Dosage Forms: n.a.
• Other Brand Names: Agrylin

Reduction of elevated platelet counts and associated risk of thromboembolic and hemorrhagic events in patients with thrombocythemia secondary to essential thrombocythemia (ET) and other myeloproliferative disorders. Has been designated an orphan drug by FDA for the treatment of ET.

Management of ET generally based on a risk-stratification approach. Treatment with a cytoreductive agent (e.g., anagrelide, hydroxyurea) usually reserved for patients at high risk (i.e., age >60 years, previous history of thrombosis, and/or platelet count ≥1,500,000/mm3) of developing thromboembolic and/or hemorrhagic complications. Some clinicians also recommend cytoreductive therapy in intermediate-risk ET patients (e.g., 40–60 years of age, platelet count >1,000,000/mm3, and cardiovascular risk factor [smoking, arterial hypertension, hypercholesterolemia, or diabetes mellitus] or familial thrombophilia).

Hydroxyurea (often combined with low-dose aspirin) generally considered drug of choice in high-risk patients with ET because of proven efficacy and infrequent acute toxicity. However, because of potential leukemogenic effects with hydroxyurea when used long term or sequentially with other cytotoxic drugs, anagrelide or interferon alfa suggested as alternative therapy in high-risk patients, particularly younger patients (<40–60 years of age), and in those who do not respond to or cannot tolerate hydroxyurea. Consider cautious use of low-dose aspirin concomitantly with anagrelide based on relative risks of thrombosis and arterial hemorrhage in individual patients. (See Specific Drugs or Foods under Interactions.)

• Generic Name: naloxone
• Dosage Forms: n.a.
• Other Brand Names: Narcan, Evzio

Treatment of opiate-induced depression, including respiratory depression, caused by natural and synthetic opiates such as anileridine, codeine, diphenoxylate, fentanyl, heroin, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, concentrated opium alkaloids hydrochlorides, and propoxyphene.

Useful for the treatment of opiate-induced depression, including respiratory depression, caused by certain opiate partial agonists including butorphanol, nalbuphine, pentazocine, and cyclazocine. However, reversal of respiratory depression resulting from overdosage of opiate partial agonists may be incomplete and require higher or more frequent naloxone doses.

May be used in community (nonmedical) settings for emergency treatment of known or suspected opiate overdosage, as manifested by respiratory and/or CNS depression. Availability as auto-injector and nasal spray facilitates administration by family members or other caregivers; such treatment is not a substitute for emergency medical care.

Early efforts to expand naloxone availability focused largely on community-based programs for substance users. Experts also support greater access by individuals being treated for opiate use disorder and their family members; patients receiving opiate analgesic therapy who are at increased risk of opiate overdosage (e.g., those with a history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate daily [or equivalent], those receiving benzodiazepines or other sedatives concomitantly, those with medical conditions that could increase sensitivity to opiate effects); first responders (e.g., emergency medical service personnel, police officers, fire fighters); and workers in other settings where overdoses may be witnessed (e.g., nursing homes, home visiting nurses, school nurses and college campuses, outreach programs, substance abuse treatment programs, halfway houses, homeless shelters, correctional facilities).

Useful for the treatment of mild or moderate as well as severe opiate-induced respiratory depression.

Administration should be accompanied by other resuscitative measures such as administration of oxygen, mechanical ventilation, or artificial respiration.

Duration of respiratory depression following opiate agonist overdosage may be longer than the duration of naloxone action and other more immediate supportive and symptomatic treatment also should be initiated.

Use in patients physically dependent on opiate agonists may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist (naloxone) persists.

If opiate abstinence syndrome is precipitated by naloxone, symptoms will be apparent within a few minutes and maximal within 30 minutes after administration; effects usually will be more severe than those following withdrawal of the opiate agonist.

Some value in the management of buprenorphine overdosage but should not be relied on for treatment of respiratory depression. Reversal of agonist effects develops slowly.

Aid in the diagnosis of suspected acute opiate overdosage (e.g., in the absence of confirmatory history and/or definitive diagnostic clinical findings).

Has been used as an aid in the diagnosis of chronic opiate abuse, but preferable to use chemical methods to detect the presence of opiates in urine, since naloxone may precipitate severe withdrawal symptoms in patients physically dependent on opiates.

Screening test (the naloxone challenge test) prior to induction of naltrexone therapy for opiate cessation in patients formerly dependent on opiates who have completed detoxification. Such screening can avoid precipitating opiate withdrawal following administration of naltrexone.

Has been used to reverse clonidine-induced coma and respiratory depression.

A combination of methadone hydrochloride and naloxone hydrochloride in a ratio of 20:1 has been administered orally in the detoxification or maintenance treatment of opiate dependence in conjunction with appropriate social and medical services.

May prevent opiate euphoria and thus decrease the desire for opiates.

Has been used for rapid or ultrarapid detoxification in the management of opiate withdrawal in opiate-dependent individuals, both in inpatient and outpatient settings.

Rapid opiate detoxification involves the administration of opiate antagonists such as naloxone and/or naltrexone to shorten the time period of detoxification.

Ultrarapid detoxification is similar, but involves the administration of opiate antagonists (i.e., naloxone, naltrexone) while the patient is sedated or under general anesthesia.

Risk of adverse respiratory and cardiovascular effects associated with this procedure must be considered as well as the costs of general anesthesia and hospitalization.

Used orally in fixed combination with pentazocine hydrochloride or sublingually or intrabuccally in fixed combination with buprenorphine hydrochloride to minimize abuse potential of pentazocine or buprenorphine; antagonistic effect of naloxone will predominate if the combinations are administered parenterally and/or if usual oral doses are exceeded.

Has been used as adjunctive therapy in a limited number of patients to increase BP in the management of septic shock. Rise in BP may last up to several hours, but not shown to improve survival. Not included in current Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock.